November/December 2018 - Advances in Neurology

Nov/December 2018

Doctors Metro MetroDoctors THE JOURNAL OF THE TWIN CITIES MEDICAL SOCIETY

Advances in Neurology

In This Issue: 0 0 0 0

Kottke Receives MMA President’s Award Dr. Pete Dehnel Public Health Fellowship Kicks Off Health Care Directives Now in Arabic and Chinese Luminary of Twin Cities Medicine

“Your patients will thank you for referring them to Dr. Crutchfield.”

A FAC E O F A M I N N E SOTA DE R M ATOL O GIST Recognized by physicians and nurses as one of the nation’s leading dermatologists, Charles E. Crutchfield III MD has received a significant list of honors including the Karis Humanitarian Award from the Mayo Clinic, 100 Most Influential Health Care Leaders in the State of Minnesota (Minnesota Medicine), and the First a Physician Award from the Minnesota Medical Association, for positively impacting both organized medicine and improving the lives of people in our community. He has a private practice in Eagan and is the team dermatologist for the Minnesota Twins, Wild, Vikings and Timberwolves. Dr. Crutchfield is a physician, teacher, author, inventor, entrepreneur, and philanthropist. He has several medical patents, has written a children’s book on sun protection, and writes a weekly newspaper health column.

Dr. Crutchfield regularly gives back to the Twin Cities community including sponsoring academic scholarships, camps for children, sponsoring programs for children with dyslexia, mentoring underrepresented students from the University of Minnesota, and establishing a Dermatology lectureship at the University of Minnesota in the names of his parents, Drs. Charles and Susan, both pioneering graduates of the U of M Medical School, class of 1963.

As a professor, he teaches students at both Carleton College and the University of Minnesota Medical School. He lives in Mendota Heights with his wife Laurie, three beautiful children and two hairless cats.

AES

THET I C

L OF APPROVA L SEA

CRUTCHFIELD DER MATOLOGY Experience counts. Quality matters.

Mayo Clinic Medical School Graduate | University of Minnesota Dermatology Trained Top Doctor Minneapolis St. Paul Magazine | Best Doctors for Women Minnesota Monthly Magazine Team Dermatologist for the Minnesota Twins, Vikings, Timberwolves and Wild 1185 Town Centre Drive, Suite 101, Eagan | 651.209.3600 | www.CrutchfieldDermatology.com

CONTENTS VOLUME 20, NO. 6 NOVEMBER/DECEMBER 2018

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LETTERS IN THIS ISSUE

Neuroscience Update

By Robert R. Neal, Jr., MD

6

PRESIDENT’S MESSAGE

Poverty: What’s a Physician to Do...and Why Bother?

By Thomas E. Kottke, MD

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TCMS IN ACTION

By Ruth Parriott, MSW, MPH, CEO Page 32

ADVANCES IN NEUROLOGY

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s

Neuromodulation in Neurosurgery, a Stimulating Topic

By Michael C. Park, MD, PhD

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s

SPONSORED CONTENT:

Multiple Sclerosis and New Immunologic Treatments

By Andrew L. Smith, MD, MHA and Flavia Nelson, MD

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s

Colleague Interview: A Conversation with Jerrold Vitek, MD, PhD

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s

Recent Advances in the Treatment of Headaches

By Abby Metzler, MD

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SPONSORED CONTENT:

Page 12

The Rapidly Evolving Landscape of Contemporary Ischemic Stroke Care

By Haitham M. Hussein, MD, MSc, FAHA s

The Chronic Effects of Neurotrauma: Is it Not as Simple as CTE?

By Uzma Samadani, MD, PhD, and Mohit Uppal

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Post-traumatic Stress Disorder Symptoms, Susceptibility and Treatment

By Rick Krueger MA, LPCC, LADC, CBIS, and John E. Simon, MD

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The Pleasure Reward System

By Jeffery Morgan, MD

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Environmental Health — Environmental Neurology

By Bruce D. Snyder, MD, FAAN

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Dr. Pete Dehnel Public Health Advocacy Fellowship Launches

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Sr. Physicians Association/ In Memoriam

30

Bounce Back Conference/ Career Opportunities

32

LUMINARY OF TWIN CITIES MEDICINE

Page 7

Page 28

MetroDoctors

Lyle A. French, MD, PhD

The Journal of the Twin Cities Medical Society

Nov/December 2018

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Doctors Metro MetroDoctors THE JOURNAL OF THE TWIN CITIES MEDICAL SOCIETY

Advances in Neurology

In This Issue: 0 Kottke Receives MMA President’s Award 0 Dr. Pete Dehnel Public Health Fellowship Kicks Off 0 Health Care Directives Now in Arabic and Chinese 0 Luminary of Twin Cities Medicine

Unlocking the mystery of the brain is an ever-evolving science with significant advancements occurring in the field of Neurology almost daily. Our authors describe several new treatment modalities being researched and in practice. Articles begin on page 8.

November/December 2018

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Doctors MetroDoctors THE JOURNAL OF THE TWIN CITIES MEDICAL SOCIETY

Physician Co-editor Peter J. Dehnel, MD Physician Co-editor Thomas E. Kottke, MD Physician Co-editor Robert R. Neal, Jr., MD Physician Co-editor Marvin S. Segal, MD Physician Co-editor Richard R. Sturgeon, MD Physician Co-editor Charles G. Terzian, MD Medical Student Co-editor Mac Garrett Medical Student Co-editor James Pathoulas Managing Editor Nancy K. Bauer Production Manager Sheila A. Hatcher Advertising Representative Erica Nelson Cover Design by Annie Krapek MetroDoctors (ISSN 1526-4262) is published bi-monthly by the Twin Cities Medical Society, 1300 Godward Street NE, Broadway Place West, Suite 2000, Minneapolis, MN 55413. Periodical postage paid at St. Paul, Minnesota. Postmaster: Send address changes to MetroDoctors, Twin Cities Medical Society, 1300 Godward Street NE, Broadway Place West, Suite 2000, Minneapolis, MN 55413.

To promote its objectives and services, the Twin Cities Medical Society prints information in MetroDoctors regarding activities and interests of the society. Responsibility is not assumed for opinions expressed or implied in signed articles, and because of the freedom given to contributors, opinions may not necessarily reflect the official position of TCMS.

November/December Index to Advertisers TCMS Officers

President: Thomas E. Kottke, MD President-elect: Ryan Greiner, MD Secretary: Andrea Hillerud, MD Treasurer: Sarah Traxler, MD Past President: Matthew A. Hunt, MD TCMS Executive Staff

Ruth Parriott, MSW, MPH, CEO (612) 362-3799; rparriott@metrodoctors.com Nancy K. Bauer, Associate Director, and Managing Editor, MetroDoctors (612) 623-2893; nbauer@metrodoctors.com Karen Peterson, Executive Director, Honoring Choices Minnesota (612) 362-3704; kpeterson@metrodoctors.com Lynn Betzold, Program Coordinator, Honoring Choices Minnesota (612) 362-3703; lbetzold@metrodoctors.com Trish Greene, Administrative Specialist, Honoring Choices Minnesota (612) 362-3705; tgreene@metrodoctors.com Amber Kerrigan, Project Coordinator, Physician Advocacy Network (612) 362-3706; akerrigan@metrodoctors.com Annie Krapek, Program Manager, Physician Advocacy Network (612) 362-3715; akrapek@metrodoctors.com Linda Singh, Executive Director, End in Mind (612) 362-3724; LSingh@endinmindproject.org Katie Snow, Administrative Coordinator, End in Mind (612) 362-3739; KSnow@endinmindproject.org

Crutchfield Dermatology.....................................

Inside Front Cover Entira Family Clinics .......................................30 Fairview Health Services .................................31 HealthPartners....................................................23 Honoring Choices MN ........................................

Outside Back Cover Lakeview Clinic .................................................31 Minneapolis Clinic of Neurology .................. 2 MN Academy of Family Physicians ............28 Noran Neurological Clinic .............................19 obimages.net ......................................................... 3 Schuster Clinic ...................................................26 St. Cloud VA Medical Center ............................

Inside Back Cover University of Minnesota Health ..................... 4 U of M School of Nursing .............................27 Vinland National Center ................................13

Send letters and other materials for consideration to MetroDoctors, Twin Cities Medical Society, 1300 Godward Street NE, Broadway Place West, Suite 2000, Minneapolis, MN 55413. E-mail: nbauer@metrodoctors.com.

For advertising rates and space reservations, contact: Erica Nelson 4084 Jana Ave. NE St. Michael, MN 55376 phone: (763) 497-1778 fax: (763) 497-8810 e-mail: erica@pierreproductions.com MetroDoctors reserves the right to reject any article or advertising copy not in accordance with editorial policy. Advertisements published in MetroDoctors do not imply endorsement or sponsorship by TCMS. Non-members may subscribe to MetroDoctors at a cost of $15 per year or $3 per issue, if extra copies are available. For subscription information, contact Nancy Bauer at (612) 623-2893.

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November/December 2018

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LETTERS

Dear Marvin, Tom, and Nancy Getting a hard copy of your current, neat MetroDoctors, I’ve reread your piece on that issue’s “luminosity.�

I’m surmising, based on the chance contact between Marvin and my assistant Nola Fortner, that this might have been considered likely a “memorial,� due to my perilous state a couple of months ago.

It’s so thoughtful you composed it and, I assure you, it’s pleasant to survive to read it!

Marvin got my evolution through education, the clinic, practice, research, teaching; then to the concept of the predominant sociocultural determinants of epidemic chronic diseases, then their interaction with genetic inuences to determine the individuals stricken in their culture.

The clue to this evolution that Marvin didn’t ďŹ nd out about was the experience I had early with medical missionary friends who, for example, told me they’d never seen a heart attack, not even a case of appendicitis in 30 years in the Congo.

Then, there was my own experience setting up mission clinics in rural Cuba under Batista, where all the mass diseases were related to poverty, ignorance, superstition, and oppression. That was followed by three years in DP camps in central Europe where again the major impediments to their immigration to the U.S. were the common diseases from exposure to persecution and wartime privations. None of these issues were effectively approachable through medical diagnosis or systems of care.

They were in the population, on the population, epidemiology more than medical. Their causes and prevention lay in lifestyle and exposures in the culture.

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Those experiences inuenced my jumping at Ancel Keys’s underpaid offer to join his adventures when I ďŹ nished residency (over the considerable annoyance of CJ Watson who wondered what I wanted to do, compared to what he offered, “with those weird guys doing those weird things over in that weird place under Memorial Stadium!â€? No Luminosity there!

You got the music stuff right, too, Marvin, but one performance was crucial to the thrill of moving an audience to joy!

The little Florida Youth Orchestra I played violin with all summer of 1934 concluded the season with a concert in the Quonsets of the CCC Camp (black), laborers accessing the pre-Columbian environs of Myakka State Park in west Florida. In the kerosene lamps all our little honkey orchestra could see from the stage was the bright teeth and eyeballs. Our wretched sounds eventually reached a happy crescendo with Dvorak’s Hungarian Dance #5.

The whole gang stood smiling and cheering and banging their enamel cups on the tables! We were forever smitten-thrilled.

And, of course, as a dry academic since, it became my joy, with small groups playing New Orleans music, to occasionally move people to smile, swing, and sway, something an academic rarely does for his faculty and staff!!

Your recognition of these happy dualities was thoughtful, kind, and, for me, still alive, delightful.

Thanks, Henry

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Physicians Serving Physicians is an independent, physician-centric organization that was established in 1981 by a group of physicians in recovery to help other physicians and their families struggling with chemical dependency. The core of PSP’s mission is to provide active help and service to physicians (including residents), medical students and their family members affected by alcohol and drug addiction.

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For conďŹ dential assistance: s #ALL EMAIL psp@metrodoctors.com s *EFFREY -ORGAN -$ )NTERIM Medical Director,

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November/December 2018

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is for kids’ hearts The first choice for second chances The Heart Center at University of Minnesota Masonic Children’s Hospital, brings help and hope to pediatric heart patients. We’re saving lives through innovation— leading the nation in developing new treatment methods for kids of all ages.

We provide outstanding care for advanced heart failure, including mechanical circulatory support, ventricular assist devices and transplant. Our history of exceptional patient outcomes led to our designation as the Twin Cities’ only LifeTrac Center of Excellence and Children’s Cardiomyopathy Foundation Center of Care.

We’re pleased to welcome Dr. Massimo Griselli to our care team. As one of the most experienced pediatric heart surgeons in the nation, Dr. Griselli will help us continue giving kids a second chance.

Visit: MHealth.org /HeartCenter Call: 888-KIDS-UMN (888-543-7866)

The University of Minnesota Health brand represents a collaboration between University of Minnesota Physicians and University of Minnesota Medical Center. © 2018 University of Minnesota Physicians and University of Minnesota Medical Center.

IN THIS ISSUE...

Neuroscience Update

T

he field of Neurology is undergoing rapid growth in both knowledge and treatments. In this issue of MetroDoctors, we have chosen articles that cover many of the newest modalities that allow more control of neurological diseases.

One of the most innovative advancements in Neurosurgery is neuromodulation where an electrical or chemical stimulus is delivered to a specific neurological site. Dr. Michael Park, in his article, discusses the use of deep brain, spinal cord and vagus nerve stimulation to greatly increase our ability to help patients with Parkinson’s, epilepsy, and spinal cord pain.

Multiple Sclerosis is the most common demyelinating disease and has mostly been treated by injections to control relapses, not its progressive tendency. MS is presumed to be an autoimmune disease which has produced the development of several interesting new drugs that can modify the disease through the immune system. Drs. Andrew Smith and Flavia Nelson lead us through the intricacies and drug options, their side effects and modes of action.

Our Colleague Interview is with Dr. Jerrold Vitek, chairman of the department of Neurology, University of Minnesota.

He emphasizes the rapid progression of advancements in the field of Neurology.

Headache is certainly a major health problem. In her article, Dr. Abby Metzler states that headache is the 4th or 5th most common reason for emergency room visits. She brings us up-to-date on both the management of headaches and their prevention. She discusses a new Botulinum drug and an exciting new class of monoclonal antibody drugs for migraines called CGRPs. Other topics include transcranial magnetic stimulation and cranial nerve electrical stimulation.

Ischemic stroke management has evolved rapidly in the last few years. Dr. Haitham Hussein provides the article on this subject. He emphasizes the changes in mechanical thrombectomy guidelines, new thrombolytic therapy, and new devices now available for stroke prevention, all of which have improved outcomes. Increased recognition of atrial fibrillation, especially with prolonged monitoring, is important for stroke prevention. Will the new Apple watch with an ECG monitor be an important tool?

By Robert R. Neal, Jr., MD Member, MetroDoctors Editorial Board

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Neurotrauma is a hot topic now especially at the VA and in sports arenas.

Uzma Samadani, MD and Mohit Uppal thoughtfully discuss the current understanding of both Traumatic Brain Injury (TBI) and Chronic Traumatic Encephalopathy (CTE).

They point out that the two are not synonymous.

As CTE is a pathological diagnosis, its research is relatively new, and its evolution is not well understood. Information on the long-term effects of TBI and its acute and chronic management are included.

Our knowledge of PTSD is rapidly expanding. Dr. John Simon and his colleague Rick Krueger state in their article that 7% of the people in the USA will suffer from PTSD in their lifetime. Many of those with PTSD have also had a traumatic brain injury (TBI) and one-half of those with TBI have substance abuse. This article leads us through the management of this complex system, outlines the genetic and epigenetic facets, and current treatments including cognitive behavior therapy and chronic processing therapy.

Addictions are an important health problem as was pointed out in our Spring 2017 issue. Dr. Jeffery Morgan provides an excellent discussion of how chemicals act on the brain through the pleasure reward system. As prescribers of drugs and caregivers for patients with addictions, it is important to understand the workings of this system. The author states that each of us uses the pleasure reward system from moment to moment to create our feelings. Has your PR system ever been hacked? Read on.

Dr. Bruce Snyder discusses the prevalence of environmental toxins and how they affect the nervous system. As the part of our scientific community that cares for the health of the people, we need to do our part to prevent harmful pollution.

Lastly, our Luminary tribute. Lyle French, MD, is a titan in the Neurology field. Our esteemed biographer, Marv Segal, nicely illustrates his service to medicine and the field of Neurology.

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President’s Message

Poverty: What’s a Physician to Do...and Why Bother?

THOMAS E. KOTTKE, MD

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n 1848, the pioneering pathologist, Rudolf Virchow, identified poverty as the root cause of the typhus epidemic in Upper Silesia — poor housing, lack of sanitation, starvation, lack of education, and hazardous working conditions were the hallmarks. He concluded that the outbreak could not be solved by treating individual patients with drugs.

In 1974, the Canadian Minister of National Health and Welfare, Marc Lalonde, dropped a bombshell with his report, “New Perspectives on the Health of Canadians.” Dividing the determinants of health into four broad categories — human biology, environment, lifestyle, and healthcare organization — he observed that, “the organized healthcare system can do little more than serve as a catchment net for the victims [of lifestyle and the environment].”

This year, Victor Fuchs echoed Virchow and Lalonde in a JAMA commentary when he suggested that U.S. health care is efficient in addressing quality-of-life tasks like knee replacement, but “exogenous morbidities” are causing the U.S. to fall behind other developed countries in prolonging life expectancy. Poverty is one of the exogenous morbidities Fuchs names.

But if American physicians deliver health care efficiently, is it their job to bother about poverty? The answer is “Yes,” and there are at least three reasons why: bothering about poverty improves the health of patients; bothering about poverty improves the health of a community’s business economy; and, bothering about poverty improves the health of the healthcare industry. When people rise out of poverty they no longer need to rely on expensive social services, they start paying taxes, and they have disposable income to spend.

So what can a doctor do about poverty? 120 years ago Virchow improved the health of both rich and poor Berliners by advocating for a sewer system. If, perchance, you live on a lake where the water is polluted by failing septic systems, you could do the same for your neighbors. Or, you could strike at the heart of poverty and advocate for the livable wage. Even if you are unwilling to do either of these, you have many, many other opportunities. My top 7 suggestions are: 9 Show your colleagues, patients, friends and community business leaders the evidence that poverty must be addressed if the health, well-being, and economic vitality of your community is to improve.

9 Prevent poverty for women by providing access to sexual health services and contraception: The ability of a woman to delay pregnancy until she has completed her education reduces the odds of poverty for two.

9 Reduce poverty by promoting literacy for all: Advocate for high-quality early childhood education; implement Reach Out and Read in your practice; and, if you can to do even more, teach adults to read, too.

9 Invest in affordable housing funds: Affordable homes enable workers to relocate for jobs and invest in their individual futures. As their income increases, they will spend some of it in the retail markets.

9 Promote clean energy: Polluted air and polluted water disproportionately burden the health of the residents of low income communities, further threatening educability, employability, and economic stability.

9 Advocate for walkable and bikeable communities: Physical activity is foundational for health, and walking and biking cost little.

9 Support Tobacco 21 and the reclassification of menthol as a tobacco flavoring: the tobacco industry targets communities of youth, LGBTQ+, and color — communities that can little afford the economic burden of tobacco.

Many of these activities are Twin Cities Medical Society programs; get active with us. And if you tackle my top 7 and still have energy at the end of the day, do what Rudolph Virchow and our colleagues Scott Jensen and Matt Klein did — run for elected office and win so that you can make an even larger impact on poverty!

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TCMS IN ACTION RUTH PARRIOTT, MSW, MPH, CEO

TCMS Makes a Splash at MMA Annual Conference Twin Cities Medical Society members were out in full force at the recent MMA Annual Conference in St. Paul, showing their commitment to making Minnesota the best place to practice medicine. Twelve policy issues were discussed during an engaging open issues forum, and nine of the 12 were articulately presented by TCMS members. The medical student section was particularly visible and well-organized, with members not only introducing their own resolution but thoughtfully commenting during each debate. The issues were prioritized by the attendees and will now be considered by the MMA Policy Council for possible adoption as standing policy.

The House of Delegates met for the last time as they considered and approved a motion to sunset the House and rely upon the MMA Policy Council to study and recommend policy issues on a timely basis throughout the year. The 38 TCMS delegates were frequently at the microphones to lend their voice to the debate.

At right is a photo of Dr. Laurel Ries, a family medicine physician at HealthEast Rice Street Clinic and first time delegate, expressing her thoughts on the motion and the needs of organized medicine moving forward.

Finally, everyone at TCMS is proud that Board President Dr. Tom Kottke was awarded the MMA’s 2018 President’s Award “in appreciation for his selfless commitment to the autonomy of physicians in the care of patients, and to the integrity of the practice of medicine.” As any reader of Dr. Kottke’s MetroDoctors columns would predict, he used every moment of his acceptance speech as a clarion call-to-action for physicians to

MetroDoctors

bring justice and equity to their communities by fighting poverty on multiple fronts.

TCMS stands ready to support Thomas Kottke, physicians as MD receives MMA they lend their President’s Award unique perspective from outgoing MMA President, George and expertise to Schoephoerster, MD. tackling some of the most difficult societal challenges that impact the health of individuals, families, and communities. Come along with us!

Medical Students Translate Health Care Directives For bilingual medical students, the opportunity to share their first language through a translation project is rewarding and beneficial. Three Chinese speakers, Monica Ngo, Minna Ding, and Elizabeth Kim have worked together to translate the Honoring Choices short-form health care directive into Chinese, and Syrian-born Peter Kassis Akal has translated it into Arabic. This project not only meets the second-year students’ independent Public Health/Health Policy requirements, but also creates new resources for Honoring Choices which will benefit Chinese and Arabic speakers throughout Minnesota.

Simultaneously it has challenged the students to examine traditional cultural beliefs about end-of-life attitudes and goals of care which can help them act as ambassadors for others learning to

The Journal of the Twin Cities Medical Society

navigate the U.S. health care system. The new translated forms will be available soon on http://www.HonoringChoices.org.

PAN Update As of October 1, 13 Minnesota communities have now adopted Tobacco 21 ordinances, including the recent additions of Minnetonka and Excelsior. We continue to see exceptional support from physicians, residents, and medical students.

This September, TCMS launched the inaugural year of the Dr. Pete Dehnel Public Health Advocacy Fellowship. (See related article on page 28.)

Physician Health and Wellness TCMS is pleased to be a co-sponsor of the Bounce Back Project/Resilience Conference: Moving from Surviving to Thriving Conference for Health Care Professionals on December 5-6, 2018 at the Crowne Plaza in Plymouth, Minnesota. (See conference flier on page 30.)

Understanding Depression and Suicide Since 2011,Twin Cities Medical Society Foundation has served as the fiscal agent for a cable television broadcast program, Understanding Depression and Suicide, co-directed and co-produced by James Jordan, MD and Mary Hanson, The Mary Hanson Show. We are proud to announce that the National Alliance on Mental Illness-Minnesota (NAMI) has agreed to “adopt” our website. The first series, Understanding Depression: Hope Through Treatment, and second series, Understanding Depression: The Suicide Connection, — along with its Spanish translation, Entendiendo la depresion: La conexion suicidio, — are now accessible via NAMI Minnesota’s website https://namimn.org/.

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Advances in Neurology

Neuromodulation in Neurosurgery, a Stimulating Topic

N

eurosurgery has historically been at the forefront of technical advances, successfully incorporating new techniques and devices to introduce new therapy and to increase safety and efficacy in the treatment of neurological diseases. In recent years, these new advances have been especially rapid in the area of neuromodulation.

Moreover, a lesser known but interesting fact is that these innovations are taking place right here in our back yard in Minnesota.

Then, what is neuromodulation?

According to the International Neuromodulation Society, therapeutic neurmodulation is “the alteration of nerve activity through targeting delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body.” Also referred to as neurostimulation, neuromodulation is a growing field in Neurosurgery which is directed at restoration of function and/ or relief of symptoms in neurological disease and includes deep brain stimulation (DBS) and response neural stimulation (RNS).

Much of the technical advances in neuromodulation are seen in DBS, a neurosurgical therapy where a thin stimulating electrode is implanted into a target area in the brain and connected to a neurostimulator device implanted under the skin in the chest usually below the collar bone. Developed in the 1980s

By Michael C. Park, MD, PhD

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November/December 2018

and first approved by the U.S. Food and Drug Administration (FDA) in 1997 for use, DBS is well known for the treatment of movement disorders such as Parkinson’s disease (PD), essential tremor (ET) and dystonia. As recently as May of 2018, the FDA approved the use of DBS in patients with medically refractory epilepsy.

The introduction of directional leads in October of 2016 for the treatment of PD and ET brought exciting new technology to DBS therapy. The newly designed DBS electrode allows the neurologist to control and “steer” the stimulation to different parts of the brain, thus enabling the treatment to be tailored to each patient in order to reduce side effects. This ability to direct stimulation is particularly advantageous when treating PD and ET. For example, in DBS for PD, the electrodes are placed in subthalamic nucleus (STN) or globus pallidus internus (GPi). When stimulating STN, the undesirable effects of stimulating the laterally located internal capsule limits the traditional DBS system as it causes muscle contraction.

Using the directional lead, neurologists can steer the stimulation medially, thus minimizing the stimulation of the internal capsule and avoiding the side effect.

When stimulating the GPi, the internal capsule is located medially and the stimulation can be directed laterally. For neurologists who treat movement disorders with DBS, this ability to control direction of stimulation is a welcome addition to the therapy.

Early to adopt this new technology and therapy, University of Minnesota Medical Center and the Departments of Neurosurgery and Neurology Movement Disorder Group was the first in the state of Minnesota to implant the DBS system with directional lead, Abbott Infinity system, in a patient with PD on January 24, 2017. As an added bonus, the new system features wireless technology for communication between the device and the controller/programmer and recently received FDA approval for MR-conditional labelling, which made the system MRI compatible.

A newly designed implantable pulse generator (IPG), introduced in December of 2017, added to the therapeutic technology options. Designed as a current source, the new IPG is able to deliver a specific and prescribed amount of current to the individual contacts of the DBS electrode. This particular device and technology was rigorously tested with a multi-center, prospective,

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double-blind, randomized sham-controlled study of DBS for PD in the U.S., the first of its kind, also known as INTREPID study. Dr. Jerrold Vitek, Chair of the Department of Neurology and the Principle Investigator for the INTREPID study said that the new device “changes the landscape of what physicians can do to help improve the quality of life for people living with Parkinson disease” and “provides an ability to sculpt the current field in the DBS target using novel technology that offers flexibility in programming,” referring to its Multiple Independent Current Control technology. With precise control of the flow of current to individual contacts, neurologists could now program a complex stimulation field to maximize therapy when stimulating STN or GPi for PD. On December 14, 2017, University of Minnesota Medical Center Movement Disorder Group became the first in the U.S. to implant the commercially available Boston Scientific Vercise DBS system.

The breakthrough advance in medical device for the treatment-resistant epilepsy is the closed-loop response neural stimulation (RNS), providing hope for patients with intractable epilepsy. Often, patients with epilepsy are evaluated for neurosurgical intervention when their disease is refractory to medication therapy. For many, surgical resection such as temporal lobectomy or amygdalohippocampectomy provides relief and seizure freedom. However, some patients are considered not to be a surgical candidate due to multiple areas of seizure foci or the seizure focus being eloquent thus not resectable, for example dominant left temporal lobe. Approved by the FDA in November of 2013 to treat medically refractory epilepsy, RNS is currently the first and only medical device that can monitor and detect the onset of seizure and respond to that activity with stimulation to control the seizure. Small electrodes are placed in the area of the brain which has been found to be responsible MetroDoctors

Table: Summary of Recent Advances in Neuromodulation/Neurostimulation Therapy Neuromodulation/ Neurostimulation

Conditions Treated

Devices and Advances

Deep Brain StimulaTION $"3

Parkinson’s disease, Essential tremor, Dystonia, Obsessive-compulsive disorder, Medically refractory epilepsy

Abbott (St. Paul, MN): directional lead, Boston Scientific (Marlborough, MA): multiple independent current control, Medtronic (Minneapolis, MN)

Response Neural 3TIMULATION 2.3

Medically refractory epilepsy

NeuroPace RNS (Mountain View, CA): closed-loop stimulation system

for seizure onset which are then connected to the neurostimulator placed within the skull. With RNS, epilepsy patients who did not have any therapeutic options for their condition are now able to undergo treatment which can control their intractable seizures. On January 20, 2015, UMMC and the Department of Neurosurgery and MINCEP Epilepsy Care implanted the first commercially available RNS system, NeuroPace, in Minnesota and the upper Midwest.

Technical advances and their incorporation into medicine, especially in the field of neurosurgery is evident. In recent years, the changes have become more frequent and it will only continue to increase. With patients and their family members having access to an increasing wealth of information and becoming their own health advocates, more patients will approach their doctors and healthcare providers with questions related to new treatments and devices for their medical conditions. Therefore, it is important that doctors and healthcare providers become familiar and keep pace with the technical advances in order to provide the best care for their patients.

The most important point is that these advanced therapies are not only here to stay but are readily offered and available for patients in Minnesota.

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Michael C. Park, MD, PhD is a board certified neurosurgeon, an Assistant Professor, MnDRIVE Neuromodulation Scholar and Director of Stereotactic and Functional Neurosurgery in the Department of Neurosurgery and Neurology at the University of Minnesota. Dr. Park received dual Bachelors in Arts and Sciences in Economics and Electrical Engineering from Cornell University in Ithaca, NY in 1992, and received Bachelors in Arts in Biology from University of Kansas in Lawrence, KS in 1994. He then received his MD and PhD from the School of Medicine and Graduate Studies, Department of Molecular and Integrative Physiology, at the University of Kansas in Kansas City, KS in 2002. He then completed his neurosurgery residency at Brown University/Rhode Island Hospital in 2009. He was awarded the prestigious William P. Van Wagenen Fellowship from the American Association of Neurological Surgeons and completed his fellowship with Dr. Jean Régis at the Université de la Méditerranée Aix-Marseille II, Assistance Publique L’Hôpital d’Adulte de la Timone in Marseille, France, in 2010. He was an Assistant Professor and the Director of Functional Neurosurgery and Pain in the Department of Neurosurgery at University of Louisville until 2014 when he joined the Department of Neurosurgery at the University of Minnesota.

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Sponsored Content

Multiple Sclerosis and New Immunologic Treatments Contributed by Andrew L. Smith, MD, MHA and Flavia Nelson, MD

The treatment of multiple sclerosis (MS), the most common demyelinating disease of the central nervous system (CNS), has evolved significantly over the past few years. The days when injections were the only treatment option have passed. While injectables remain an important component of treatment, oral and infusion therapies for MS provide patients with more options and higher efficacy, although sometimes with a higher risk for side effects and potential safety issues.

Additionally, there is renewed excitement about the use of autologous hematopoietic stem cell transplantation. Over the course of this article, we’ll review these newer MS treatment options.

Multiple sclerosis is divided into three subtypes: relapsing remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), and primary progressive multiple sclerosis (PPMS). RRMS is characterized by episodes of neurologic dysfunction that come on over hours to days and gets better over weeks to months. These episodes are called exacerbations or relapses and are unpredictable. After 15 years, roughly half of the patients with RRMS will stop having relapses and slowly develop disability. This slow accumulation of disability is called SPMS. PPMS is diagnosed if the patient never has a relapse and just slowly develop disability over time. To date, we have treatments for PPMS and RRMS, which we will begin to review now.

Oral Therapies Currently three oral disease-modifying therapies (DMTs) for the treatment of RRMS are FDA approved. Teriflunomide (Aubagio), dimethyl fumarate (Tecifera), and fingolimod (Gilenya) have already helped hundreds of thousands of MS patients across the globe.

Each medication is unique. Finding the right 10

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Andrew L. Smith, MD, MHA

Flavia Nelson, MD

medication for an individual patient depends on the patient’s goals, response to previous treatments, and current disease stage. Treatment decisions are carefully made on a caseby-case basis as every MS patient is different.

A switch to a newer DMT should always be preceded by a detailed discussion with the patient’s neurologist in order to assess the benefit-risk ratio for each individual.

Teriflunomide. Teriflunomide, it’s believed, works by blocking an enzyme needed to create new lymphocytes, which become activated by RRMS and attack the brain. By doing so, it prevents the immune system from ramping up to damage the brain. Its effectiveness against RRMS was proven in the TEMSO and TOWER clinical trials, which showed respectively a 31.2% and 36.3% decrease in the number of relapses per year compared to those in placebo-treated MS patients.1,2 This therapy is not for those with liver disease or tuberculosis, and patients considering becoming pregnant should probably opt for a different therapy.

Care monitoring by an expert is needed for this therapy.

Dimethyl fumarate. It is uncertain exactly how dimethyl fumarate works, but it appears to decrease inflammation and promote neuroprotection. Treatment with dimethyl

fumarate has been proven effective in RRMS in the DEFINE and CONFRIM trials.

These studies found a 44% and 53% decrease in the number of relapses per year compared to those in placebo-treated patients, and 18-28% of patients were free of disease activity (similar to being in remission) by the end of the trial.3,4,5 Dimethyl fumarate generally causes mild to moderate side effects of flushing and gastrointestinal symptoms that most patients tolerate well. Very rarely, this medication can cause a drop in the number of white blood cells that could potentially lead to opportunistic infections like progressive multifocal leukoencephalopathy (PML), a potentially fatal brain infection caused by the John Cunningham virus. It is important for patients to be monitored for these potential risks.

Fingolimod. Fingolimod binds to molecules in the surface of lymphocytes and prevents brain damage by keeping inflammatory cells from escaping the lymph nodes and migrating to the brain. In the TRANSFORMS and FREEDOMS trial, fingolimod reduced the number of relapses per year in RRMS, improving on results with Rebif (interferon beta-1a) by 38% and on placebo results by 48%; 33% of patients achieved freedom from disease activity.3,6,7 It is the first and only MS therapy approved for use in pediatric patients. In the PARADIGMS trial, fingolimod reduced the number of relapses per year in children by 81.9% compared to results with Rebif. Fingolimod’s main side effects are bradycardia during first and second dose administration, macular edema, and worsening reactive airway disease. Additionally, this medication can put patients at risk for opportunistic infections like PML. Therefore, it is important for patients to be closely monitored while on this medication.

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In an exciting development, similar agents with fewer cardiac side effects, Ozanimod and Siponimod, should be FDA approved within the next year as RRMS and SPMS treatments respectively.

Infusions The infusion therapies natalizumab (Tysabri), ocrelizumab (Ocrevus), and alemtuzumab (Lemtrada) are highly effective IV therapies for MS. All are monoclonal antibodies specifically designed to target molecules to minimize MS disease activity and require dosing as seldom as once a year. For MS patients, the freedom from having to frequently take a pill or shot is highly desirable; however, due to these therapies’ slightly higher safety risk, they are most often utilized in MS centers like University of Minnesota Health’s.

Natalizumab. Natalizumab works by binding to a molecule in the blood brain barrier, which prevents inflammatory cells from entering the CNS. In the AFFRIM trial, this highly effective therapy for RRMS reduced the number of relapses per year by 68% over that offered by the control. Natalizumab-treated patients achieved freedom from disease activity 37% of the time.3,8 While this therapy presents a risk of PML, advanced blood work can accurately predict this risk.

Through careful patient selection, patients can remain on this therapy indefinitely as long as they have not been exposed to the virus that causes PML. New strategies like increased interval dosing further reduces the risk of PML. Patients also need to be monitored for alterations in liver function and reactions to the infusion. Care is also needed when stopping this therapy, because of the risk of potential rebound disease that can occur in a third of patients. This once every 28-day therapy should be supervised, preferably by certified MS providers like those at the University of Minnesota Health MS clinic.

Ocrelizumab. Ocrelizumab is somewhat unique because it can treat both RRMS and PPMS. This medication is believed to destroy B cells, which are believed to play a critical role in presenting self-antigens and making antibodies that aid in the damage of the brain and spinal cord in MS. In RRMS trials OPREA 1 and 2, 47.5 and 47.9% of patients were disease activity free after treatment, and the therapy achieved a 46% and 47% decrease in the number of relapses MetroDoctors

per year compared to results with Rebif in their respective trials.3,9 In the PPMS trial ORATORIO, patients on treatment had a 29.6% risk of not developing disability worsening when compared to placebo.10 Prior to therapy, it is important for patients to be checked for previous exposure to certain viruses and infections that can be exacerbated by the therapy. This medication may also pose a slightly increased risk of breast cancer. For these reasons, this medication should be prescribed by someone familiar with MS care.

Alemtuzumab. Alemtuzumab targets and destroys most B and T cells. Similar to rebooting a computer after getting a blue screen, alemtuzumab allows the immune system to shut down and “restart” or reconstitute itself. Typically, it takes about a year for the immune system to be fully reconstituted.

In the CARE-MS1 and CARE-MS2 trials, the number of relapses per year was reduced by 49.4%-54.9% compared to results Rebif, with 32-39% of patients on the therapy achieving remission.3,11,12 Interestingly, Lemtrada, the trade name of alemtuzumab prescribed for relapsing MS, appears to have a durable effect, with roughly half the patients not requiring treatment after the first year.

The main risk of alemtuzumab is patients developing a new autoimmune disease while their immune system is rebooting. Patients, therefore, require monthly blood monitoring for 4 years after the last dose. Alemtuzumab is offered through University of Minnesota Health. Those prescribing Lemtrada must have special training and certification, and the ability to prescribe it is typically restricted to MS centers with extensive expertise.

Stem Cell Transplant There is new excitement behind the old nonFDA approved therapy of autologous hematopoietic stem cell transplantation. In this therapy, immune stem cells are selectively removed from the body, and the remaining immune cells are destroyed by chemotherapy. While there are many different regimens with different levels of safety, studies suggest that 68% to 80% of patients experience durable suppression of disease activity multiple years after the transfusion.3,13 Currently, our MS clinic is set to join the handful of specialty centers in the world that offer this therapy.

Conclusion This is an exciting time for MS research, and

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University of Minnesota Health specialists are pleased to be at the forefront in offering the latest treatment options for patients. The University of Minnesota Health Multiple Sclerosis Clinic has increased its capacity by 400% and now has more locations and four neurologists with training and significant expertise in MS. In addition to providing these exciting treatments, our specialists are actively involved in clinical trials to find better treatments and to answer critical questions about the management of MS. We encourage interested patients to reach out to our group to learn about eligibility for participating in these trials and to receive the latest care.

Andrew L. Smith, MD, MHA, is a staff neurologist at University of Minnesota Health Maple Grove Clinics and its Minneapolis-based Clinics and Surgery Center, where he specializes in treating multiple sclerosis (MS) patients.

Prior to his current role at the University of Minnesota, Dr. Smith was a research intern at the National Institutes of Health in Bethesda, Maryland, where he examined the MRI process to determine how technology might be better used to make prognostic assessments in MS. Dr. Smith earned his doctorate of medicine and master of Health Administration degree at the Ohio State University in Columbus, Ohio. He completed a residency in Neurology at University Hospital Case Medical Center in Cleveland, Ohio, and a fellowship in Neuroimmunology at the Cleveland Clinic Foundation Mellen Center in Cleveland, Ohio. He is board-certified in Neurology.

Flavia Nelson, MD, is an Associate Professor of Neurology and Director of the Multiple Sclerosis Division at the University of Minnesota, Twin Cities Campus. She is active in the implementation and conduct of clinical trials on multiple sclerosis and conducts clinical research in quantitative structural and functional magnetic resonance imaging in demyelinating diseases. She received her medical degree from the University of Chihuahua School of Medicine in Mexico, followed by an Internal Medicine residency at Texas Tech University Health Science Center in El Paso, TX, and a Neurology residency, Multiple Sclerosis fellowship, and faculty appointment at the University of Texas Health Science Center at Houston. She joined the University of Minnesota faculty in 2018.

References available upon request.

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Advances in Neurology

Colleague Interview: A Conversation with Jerrold Vitek, MD, PhD

*

errold Vitek, MD, PhD is Professor and Chair, Department of Neurology, and Director of the Neuromodulation Research Program at the University of Minnesota. Prior to this appointment, Dr. Vitek served as the Neuromodulation Research Center Director at the Lerner Research Institute of the Cleveland Clinic Foundation and held the Edward F. and Barbara A. Bell Family Endowed Chair. He also held faculty positions at Emory University AND 4HE *OHNS (OPKINS 5NIVERSITY $R 6ITEK RECEIVED BOTH A 0H$ FROM THE $EPARTMENT of Physiology and his medical degree from the University of Minnesota. He completed an internship in Medicine at Mary Imogene Bassett Hospital, Cooperstown, NY and a residency IN .EUROLOGY AT 4HE *OHNS (OPKINS (OSPITAL "ALTIMORE -$

Has Neurology changed during your career?

Yes, quite signiďŹ cantly. It used to be said that in Neurology we could diagnose disorders but were limited in our ability to treat them; that is no longer the case. Many new therapies for a multitude of neurological disorders have been developed over the years.

Infusion therapies for multiple sclerosis and neuromuscular disorders, deep brain stimulation for Parkinson’s disease, intractable tremor and dystonia, interventional treatment of ischemic stroke are just a few of the many new developments in our treatment armamentarium.

What is unique about the Department of Neurology at UMN? What are you most proud of?

We have a very talented group of individuals who sincerely care about our patients and work extremely well together. A signiďŹ cant number of our faculty are on the front line of developing new therapies either in the laboratory working in the basic sciences or running clinical trials. We have more than doubled in size since 2010 and continue to grow new clinical programs and strengthen 12

November/December 2018

research in the department. We have a signiďŹ cant breadth of expertise in a variety of neurological disorders including movement disorders, epilepsy, multiple sclerosis, stroke, neurocritical care, headache, sleep and neuromuscular disorders, neurooncology, neurobehavior and general clinical neurology.

How have the historical aspects of the Department of Neurology — from A.B. Baker, on — inuenced its present clinical and administrative function?

There is a strong emphasis on training the next generation of neurologists so education has been a mainstay in this department since it was ďŹ rst developed into a stand-alone department by A. B. Baker many years ago. There is an expectation in the department that training our future neurologists is a high priority; but, we do so with the understanding that Neurology is changing and therapies are being advanced at a pace previously not thought possible.

The evolution from working as a single discipline to collaborating with neuroscientists, our colleagues in imaging, neurosurgery, psychiatry and biomedical engineering has changed the face of how we work to understand and treat neurological disorders.

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Describe the current clinical collaboration between the Departments of Neurology and Neurosurgery.

Collaborations between our two departments have been extensive and continue to grow. These include treatment of brain tumors, stroke and endovascular, neurocritical care, epilepsy and deep brain stimulation for Parkinson’s disease, tremor and dystonia.

More and more we see the importance of utilizing the expertise that each department brings to patient care. Neuroscience service lines where physicians are aligned across departments are increasingly being developed and I believe represent the future for care in the neurosciences.

How is neurology going to be different 20 years from now?

Technology continues to develop, breakthroughs in genetics will lead to patient-specific therapy. Patients who are diagnosed with a particular disorder may have their therapy tailored based on their genetic profile, what we now call precision medicine. The growth of immunotherapy, understanding the molecular changes

in the body that underlie neurological disorders, how circuits in the brain are altered in neurological disease and new approaches to modulating these circuits to improve function are among the many novel developments that are being applied to the treatment of neurological disorders.

What does the future of Neuromodulation look like?

What started as a treatment for inherited tremor has expanded beyond our imagination when we first began performing DBS in the 1990s in the United States. The list of disorders approved for DBS now include essential tremor, Parkinson’s disease, epilepsy and there are humanitarian device exemptions for OCD and dystonia. Trials continue to explore its role in Alzheimer’s disease, addiction, depression, among other neurological and psychiatric disorders. Noninvasive approaches of neuromodulation include TMS, MRI guided focused ultrasound are also increasingly being utilized or studied for the treatment of neurological and psychiatric disorders including depression and recovery from stroke. This is a field that continues to grow at a pace that has far exceeded our original expectations.

Canoeing at Vinland’s main campus in Loretto, Minnesota

Vinland Center provides drug and alcohol treatment for adults with cognitive disabilities. We make all possible accommodations for cognitive deficits and individual learning styles.

Located in Loretto, Minnesota — just 20 miles west of Minneapolis.

) VinlandCenter.org MetroDoctors

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November/December 2018

13

Advances in Neurology

Recent Advances in the Treatment of Headaches Exciting Time for Headache Medicine

In the United States, 15% of people ages 15 to 64 report suffering from at least one migraine or severe headache in the past three months.1 In women, the frequency is even higher, with approximately one in five women suffering from severe headaches or migraines.2 The prevalence and severity of headache disorders results in healthcare utilization; in emergency departments — headache is consistently the fourth or fifth most common reason for an emergency room visit.1 Headaches can also affect quality of life, resulting in lost work hours and decreased ability to engage in social and family activities.

The goal for many patients with headache disorders is to work with their physician to develop an individualized management plan that provides adequate acute and rescue treatment, as well as preventive treatment when needed, to optimize functioning. Fortunately, this is an exciting time for headache medicine. Significant advances have increased understanding of the pathophysiology of headaches, and there are new treatment options currently available or on the horizon. These breakthroughs provide patients who are suffering from headaches with more management choices than ever before.

Advances in Acute Headache Treatment

An acute headache treatment plan should be stratified and individualized to the

By Abby Metzler, MD

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November/December 2018

patient, while also choosing treatments with the highest likelihood of success, based on available evidence. There is strong evidence supporting the efficacy of non-specific analgesics, nonsteroidal anti-inflammatory medications, triptans, and ergots for the acute treatment of migraine, as published in Headache, in 2015.3 These medications continue to be the foundation of first-line treatment for migraine patients, the most common headache type to present to medical attention. For patients for whom these acute medications are contraindicated, adjunct therapy is required.

Or when medication overuse is a concern, peripheral nerve blocks and newer neurostimulation devices are increasingly being used as part of the treatment plan.

Peripheral nerve blocks for headache can vary in the medication administered, but typically include an anesthetic, commonly lidocaine or bupivacaine, used alone or in combination with a corticosteroid. While high quality evidence

showing efficacy of treatment is lacking for most headache types, recent expert consensus from 2013 concluded that peripheral nerve blocks are generally safe and yield significant pain improvement and can be long lasting for many headache disorders.4 Some of these peripheral nerve blocks include greater and lesser occipital nerve blocks, supraorbital nerve block, supratrochlear nerve block, auriculotemporal nerve block, or sphenopalatine ganglion block, depending on the individual patient and headache diagnosis.

Beyond acute medications and peripheral nerve blocks, three external neurostimulation devices have recently emerged as FDA-approved treatment options for headache patients. A single-pulse transcranial magnetic stimulation device was approved in 2013 for acute treatment of migraine with aura. In 2017, the device approval was expanded to include both acute and preventive treatment of migraine. Patients charge the device and self-administer the brief pulses of magnetic stimulation to the back of the head, generally twice a day and as needed. The mechanism of action is not well understood, but transcranial magnetic stimulation might treat migraine by disrupting or preventing cortical spreading depression, a phenomenon associated with migraine.5 In 2014, another device, an external trigeminal nerve stimulator, was approved for migraine prevention.

Approval for an additional indication of acute migraine treatment was then added in 2017. To use the device, an electrode is placed on the patient’s forehead, the device is magnetically attached and turned

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on, and electrical stimulation is delivered externally to the branches of the trigeminal nerve for either 60 or 20 minutes, to acutely treat or prevent migraine attacks.

External trigeminal nerve stimulation might treat migraine acutely by blocking signals in the afferent pain pathway; its utility as a preventive treatment might be secondary to neuromodulation over time.6 Finally, a non-invasive vagal nerve stimulator device was approved for treatment of episodic cluster headache in 2017 and migraine in 2018. The patient applies gel to the handheld device and places it on his or her neck over the vagus nerve; electrical stimulation strength is adjusted by the patient and is delivered over two minutes. Non-invasive vagus nerve stimulation might treat headaches acutely by blocking signals in the afferent pain pathway, with a neuromodulation effect over time to prevent attacks.7 Advances in Preventive Headache Treatment

Preventive treatment for headache has traditionally taken the form of daily medications taken whether or not a headache is present, with the goal of decreasing headache frequency, severity, and duration.

Preventive headache treatments have been borrowed from several medication classes, including anti-depressants, anti-hypertensives, anti-epileptic medications, and supplements. While these continue to be important treatment options for headache patients, newer options, including botulinum toxin and a calcitonin-gene related peptide receptor monoclonal antibody, have been FDA approved for headache prevention. These recent advances offer

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additional options for patients who have not found adequate response or cannot tolerate side effects from the longer established preventives.

In 2010, onabotulinumtoxinA, a form of botulinum toxin, was approved by the FDA for treatment of chronic migraine.

OnabotulinumtoxinA treatment is administered as a set of injections over the head, neck, and shoulders, following a chronic migraine protocol. The injections are usually completed in approximately 10 minutes. The intramuscular injections are repeated every three months, as the treatment wears off. Botulinum toxin is known to have several effects on neurons which may explain its effect on headache, including altering neurotransmitter release peripherally, and possibly indirectly attenuating central sensitization to improve chronic migraines.8 Most recently, in 2018, erenumab became the first calcitonin-gene related peptide (CGRP) receptor monoclonal antibody to be approved for prevention of migraine. Erenumab is administered as a monthly subcutaneous injection, given in either 70 mg or 140 mg doses. Erenumab is the first medication of several expected to be approved in the coming months that acts through CGRP inhibition. Many in the headache field are cautiously optimistic about the potential for this new class of medications to treat migraine in a novel way, targeting the specific CGRP ligand or receptor that is important in migraine pathophysiology and pain signaling.9 The last decade has brought about many novel treatments in the field of headache medicine. As our understanding of headache pathophysiology increases,

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promising advances in treatment will continue to become available, with the goal of reducing disability and optimizing quality of life for patients with headaches.

Abby Metzler, MD is an Assistant Professor of Neurology at the University of Minnesota. Dr. Metzler can be contacted at ametzler@umn.edu for correspondence regarding headaches. To refer a patient for headache treatment, the M Health Clinics and Surgery Center provider referral line is (612) 672-7000.

References 1.

Burch, R, Rizzoli, P, and Loder, E. The Prevalence and Impact of Migraine and Severe Headache in the United States: Figures and Trends From Government Health Studies. Headache. 2018; 58(4):496-505.

2.

Summary Health Statistics: National Health Interview Survey, 2016. CDC. Table P-1. Respondent-assessed health status, by selected characteristics: headache, United States, 2016. https://www.cdc.gov/nchs/nhis/shs/tables.htm.

Accessed September 10th, 2018.

3.

Marmura M, Silberstein S, and Schwedt, T. The Acute Treatment of Migraine in Adults: the American Headache Society Evidence Assessment of Migraine Pharmacotherapies.

Headache. 2015;55(1):3-20.

4.

Blumenfeld A, et al. Expert Consensus Recommendations for the Performance of Peripheral Nerve Blocks for Headaches – a Narrative Review. Headache. 2013;53(3):437-446.

5.

Andreou AP, et al. Transcranial magnetic stimulation and potential cortical and trigeminothalamic mechanisms in migraine. Brain.

2016;139(7):2002-2014.

6.

Schoenen J. Migraine treatment with external trigeminal nerve stimulation: current knowledge on mechanisms. Internal Medicine Review. 2017;3(4):1-16.

7.

Yuan H, Silberstein SD. Vagus Nerve Stimulation and Headache. Headache. 2017;57(1):2933.

8.

Escher, C, et al. Botulinum toxin in the management of chronic migraine: clinical evidence and experience. Ther Adv Neurol Disord.

2017;10(2):127–135.

9.

Tso, AR and Goadsby, PJ. Anti-CGRP Monoclonal Antibodies: the Next Era of Migraine Prevention? Curr Treat Options Neurol.

2017;19:27.

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Sponsored Content

The Rapidly Evolving Landscape of Contemporary Ischemic Stroke Care Contributed by Haitham M. Hussein, MD, MSc, FAHA

In 1968, Dick Fosbury won the Olympic gold medal for high jump by pioneering an entirely new approach to the sport. He modified his jumping technique, which became known as the “Fosbury Flop.”

In the field of stroke, and after years of stagnation, multiple “Fosbury Flops” have happened in a short period of time, reducing mortality and improving outcomes.

and complex resources and processes is no easy task. Hospitals with mechanical thrombectomy capabilities are now viewed as better destinations for stroke care, regardless of type and severity. A recent survey of healthcare professionals who care for acute stroke patients found the majority of emergency management services (EMS) and emergency department (ED) medical directors preferred to have patients with suspected stroke seen in hospitals with endovascular capability. This has pushed many hospitals to establish it and attempt to obtain stroke certification.

Mechanical Thrombectomy Revolution

This first occurred in 2015. MR CLEAN trial[1] researchers were the first to prove the benefit of mechanical thrombectomy in improving functional outcome after stroke as measured by the degree of independence of stroke survivors. This technique which involves the insertion of a microcatheter into a patient’s blocked vessel, then grab or suction the blood clot causing the occlusion, had been tested before but MR CLEAN was the first to perfect it and prove its value. Several subsequent trials confirmed the benefit of mechanical thrombectomy. American Heart Association and American Stroke Association (AHA/ASA) added mechanical thrombectomy to its treatment guidelines in 2015, revolutionizing stroke care. Prior to that, only one treatment was proven to benefit stroke patients: intravenous (IV) alteplase.

The mechanical thrombectomy trials helped change doctors’ attitude towards treating certain groups of patients. Historically, older patients and those with severe stroke didn’t receive IV alteplase because of the high risk of bleeding complications. However, when all mechanical 16

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Extending Treatment Windows

thrombectomy trial patients were compiled in a meta-analysis, older and more severe stroke patients benefited from the procedure even more than others.

These trials, and the updated AHA/ ASA guidelines, shook the stroke world.

This was drastically different from IV alteplase, which was indicated for ischemic stroke regardless of the size of the artery occluded and only required a non-contrast head CT and a blood glucose check.

Mechanical thrombectomy is only indicated for patients with stroke due to large vessel occlusion (LVO). Identifying these patients requires CT angiogram and a specialized neuroradiologist to review the study. The procedure itself is done in an angiography suite that needs certain staffing and equipment and highly specialized doctors: interventional neuroradiologists.

Caring for these patients after the procedure requires a specialized intensive care unit. Ensuring availability of these costly

Most mechanical thrombectomy trials used treatment windows of six to eight hours from symptom onset. But two recent trials explored longer treatment windows for mechanical thrombectomy. DEFUSE 3[2] extended the window to 16 hours, and DAWN[3] extended it to 24 hours. Both used imaging technology to quantify the volume of permanently damaged brain tissue and brain tissue at-risk of permanent damage. The results were similar and impressive. DAWN increased the rate of functional independence from 13 to 49% three months after the stroke. DEFUSE 3 increased the rate from 17 to 45%.

DEFUSE 3 became the second trial to reduce mortality after stroke. These trials are proving a new concept in stroke care: individualizing the selection of patients for treatment based on viable brain tissue, not an arbitrary time window. This, too, is a Fosbury Flop, not just because it allows the treatment of more patients, but mainly

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because it proves a new concept in stroke care by individualizing the selection of patients for treatment based on their viable brain tissue seen on advanced imaging rather than using an arbitrary time point that may or may not apply to a particular patient.

However, this approach also has challenges. Typically, patients with suspected stroke who are perceived to be within the time window for acute therapies, like IV alteplase and mechanical thrombectomy, are handled with high level of acuity by EMS and the ED. That’s about eight hours for most hospitals. Extending the window to 24 hours means EMS and ED would handle more patients with high levels of acuity, which requires more staffing, beds and equipment — all finite resources. Selecting patients for this extended window also requires sophisticated imaging with CT or MR perfusion scans that are less common. When available, they’re complex and time-consuming to perform and analyze without expensive imaging analysis software.

New Generation Thrombolytic

This year, researchers published EXTEND-IA TNK trial[4] results in the New England Journal of Medicine. It showed IV tenecteplase restored blood flow to brain tissue at-risk of damage in patients with LVO stroke better than IV alteplase.

Tenecteplase is a bioengineered thrombolytic with improved properties compared with alteplase. It has 15-fold higher fibrin specificity and 80-fold reduced binding to the physiological plasminogen activator inhibitor. It better targets the occlusion while lowering the risk of systemic bleeding. It also has a significantly longer plasma half-life, allowing for a single bolus administration rather than infusion.

Last year, a different trial, NOR-TEST,[5] showed the safety and efficacy of high dose tenecteplase is equivalent to alteplase in patients presenting with small strokes.

While it’s only a phase 3 trial, it could be a Fosbury Flop, too. Tenecteplase is easier, faster to use, cheaper, and potentially safer than alteplase.

New Options for Prevention

The role of patent foramen oval (PFO) in acute stroke has been debated for decades.

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It’s a hole connecting the right and left atria during fetal life that normally closes after birth. For about 20-25% of the general population, it never closes. Usually it poses no risk. But PFO is more prevalent in strokes of undetermined cause. This suggests it may contribute to stroke by allowing blood clots to move from the venous side of the heart to the arterial side. PFO can be closed surgically or endovascularly, but the benefit of closure on subsequent stroke risk has been debatable. Finally in 2017, three trials — RESPECT,[6] CLOSE[7] and Gore REDUCE[8] — showed that closing PFO significantly reduced the incidence of subsequent stroke in patients who present with stroke that has no other obvious cause.

Another new device closes the left atrium appendage (LAA), a small pocket on the back wall of the left atrium. It’s a common site for blood clot formation in patients with atrial fibrillation. PREVAIL,[9] an early trial, indicated it was not better than medical management because of a high rate of procedure-related complications. But a second trial, PROTECT-AF,[10] showed it had superior performance, fewer adverse events, and better stroke prevention at three years. This device would particularly help patients at high risk for bleeding on long-term anticoagulation but who can tolerate short-term anticoagulation after device deployment.

More research is needed to refine patient selection and periprocedural protocol.

Recognition of Paroxysmal Atrial Fibrillation Role in Stroke

Atrial fibrillation disrupts a person’s heart rhythm and can lead to clots within the heart and subsequent stroke. When atrial fibrillation is intermittent, it can be missed with routine EKG or short-term heart rhythm monitoring. As such, monitoring for several weeks after stroke, using external devices, is a way to search for intermittent atrial fibrillation after stroke.

Several trials, including ASSERT,[11] EMBRACE[12] and CRYSTAL AF,[13] showed that in selected populations, the longer the heart is monitored, the more paroxysmal atrial fibrillation is found.

Implantable loop recorders are gaining

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momentum in patients whose strokes are highly suggestive of cardiac source and whose external cardiac monitoring doesn’t detect atrial fibrillation. Implantable devices are convenient and have battery life of several years. A potential Fosbury Flop is preemptive cardiac monitoring in certain populations (e.g. women 65 years or older) to identify intermittent atrial fibrillation before stroke happens — similar to mammography or colonoscopy screening strategies.

Dual Antiplatelet Therapy for Secondary Stroke Prevention

The most recent advancement was the POINT trial[14] that examined the benefit of combining clopidogrel with aspirin for three months after a minor stroke or a transient ischemic attack, versus using aspirin alone. The trial showed lower rate of subsequent stroke among those using the dual therapy. However, this group also had a higher incidence of major hemorrhage.

POINT supports the results of an earlier Chinese trial, CHANCE,[15] which didn’t gain popularity in the United States. It’s notable that both used dual antiplatelets therapy for a short period. Long-term use has been associated with higher rates of life-threatening bleeding (MATCH[16]) and death (SPS3[17]).

Conclusion

After years of stagnation, treatment of acute stroke and secondary stroke prevention has rapidly evolved. Even more is expected in the near future. Looking ahead, the medical and public health community needs to improve research related to stroke prevention.

Haitham M. Hussein, MD, MSc, FAHA is a neurologist at Regions Hospital. He is Medical Director of the Regions Hospital Comprehensive Stroke Center. As a HealthPartners Institute researcher, he focuses on clinical research in the diagnosis, early treatment and secondary prevention of cerebrovascular diseases.

References available upon request.

November/December 2018

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Advances in Neurology

The Chronic Effects of Neurotrauma: Is it Not as Simple as CTE? With the increased medical and public focus on traumatic brain injuries (TBIs) and their long-term consequences in the 21st century, the need for comprehensive diagnostic and therapeutic tools has become apparent. This is particularly crucial for patients with multiple or complex TBIs, and for those who have been repetitively exposed. One approach currently being explored is the identification of factors that impact an individual’s response to TBI. Given the significant variation in response between individuals exposed to the same traumatic event, treatment and prognosis are formulated on a case-bycase basis. Previously noted predisposing factors include age and genetics. Below, we summarize contemporary literature relevant to conditions of chronic effects of neurotrauma, management strategies of such effects, and different impact factors that influence said strategies.

Chronic Effects of Neurotrauma and Chronic Traumatic Encephalopathy (CTE)

Chronic effects of neurotrauma are the symptoms and potential disabilities which arise or persist in patients after isolated or repeated head injuries. The most common cause of persistent symptoms after a blow to the head is post-concussive syndrome, which has multiple etiologies including ocular motility dysfunction, neck injury, cortical spreading depression, traumatic axonal injury, and anoxic injury among many others. In epidemiologic studies, a

By Uzma Samadani, MD, PhD, and Mohit Uppal

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single brain injury has been shown to increase the risk of affective disorder, psychiatric hospitalization, suicide, and pension disability. Multiple brain injuries are thus postulated to have even more deleterious effect. The demographic most commonly associated with these chronic repetitive sequelae are professional athletes and military personnel, both of whom Uzma Samadani, MD, PhD Mohit Uppal may be exposed to repetitive associated with increased risk for demenneurotrauma. The chronic effects of neutia. However, epidemiologic study of cirotrauma and CTE do not describe synvilians with a single isolated brain injury onymous conditions. CTE is a pathologic has not demonstrated that association. finding without a defined clinical correlate Female sex is one of the most significant that may represent one of many disease risk factors for dementia since the condiprocesses that falls under the categorization tion is twice as common in females versus of chronic effects of neurotrauma. males, despite the fact that brain injury is Research on CTE is relatively new, more common in males. The nine most and as such, many investigations of the significant reversible risk factors for dedisease are limited to retrospective analymentia are early life education; midlife ses of clinical records and post-mortem hypertension, obesity, and hearing loss; histopathology. This methodology is useful and old-age smoking, depression, physical for determining the patterns in anatomic inactivity, diabetes, and social isolation. pathology. However, many crucial pieces Civilian brain injury is only known to be of information, such as initial presentaa risk factor for dementia in men over the tion and evolution of symptomatology, age of 55 years. are often impossible to determine. CTE Among the many mechanisms by is postulated to represent the long-term which brain injury can lead to chronic consequence of diffuse axonal injury which effects, there are several conditions that results in axonal shearing, damaging the improve over time, which include axonal supporting microtubules composed of shearing and others that may cause a worstau and other proteins. The definition of ening of symptoms. Notable in this latter CTE is abnormal localization of hypercategory are conditions that are hard to phosphorylated tau proteins in particular detect and quantitate, including cortical locations within the cortex. spreading depression and heme deposition Brain injury in veterans has been MetroDoctors

The Journal of the Twin Cities Medical Society

from microhemorrhage. Neither of these pathophysiologies requires the co-existence of CTE. Management and Mitigation of Long-Term TBI Consequences

In order to mitigate the long-term consequences of brain injury, one must ďŹ rst be able to detect and quantitate the acute impact. Some aspects of brain injury, such as intracranial pressure, are relatively straightforward to quantitate, while others such as cortical spreading depression, axonal shearing, and microhemmorhage are more difďŹ cult to detect.

The phases of injury in TBI can be classiďŹ ed as primary or secondary. Primary injury is deďŹ ned as the direct central nervous system tissue damage from an external force, such as that seen after a blow to the head. Secondary injury encompasses the sequelae of the primary impact and includes swelling, decreased blood ow, and poor oxygen delivery to the brain. In

a clinical setting the goal of management for TBI patients is to reduce or prevent secondary injury. As with any disease process, in order to achieve optimal patient recovery, the development and subsequent implementation of targeted management techniques is vital.

Traditional TBI management techniques in the unconscious patient may include invasive monitoring and reduction of elevated intracranial pressure (ICP). ICP is deďŹ ned as the pressure inside the skull that is exerted on the brain tissue as well as the other intracranial contents. Since the skull is a rigid structure which cannot expand to accommodate new volumes, like those seen in swelling and hemorrhage, the pressure inside increases. This forces native contents, such as cerebrospinal uid (CSF) and venous blood, of equal volume out of the skull to compensate. If left untreated this can lead to catastrophic consequences including herniation of brain tissue out

of the skull and subsequent respiratory failure. One widely utilized method of reducing ICP is the systematic drainage of cerebrospinal uid (CSF) using a surgically implanted extraventricular drain (EVD).

A second invasive monitoring modality for the management of TBI is the measurement of brain tissue oxygenation.

Measurement of brain tissue oxygenation is the only modality associated with reduction in mortality in randomized prospective trials.

Nutritional support has also been identiďŹ ed as possibly improving patient outcomes and decreasing the risk for secondary insult. This is especially important in severe TBI as patients often require intubation and are at risk for hyperglycemia. While the body attempts to recover, it requires a signiďŹ cant amount of caloric energy. A study published in The Cochrane Database of Systematic Reviews (Continued on page 20)

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x Numbness x ƉĹ?ůĞƉĆ?LJ͏^ÄžĹ?ÇŒĆľĆŒÄžĆ? x Tremors x AlzheimerÍ›s Disease x EÄžĆľĆŒĹ?Ć&#x;Ć? x ALS x ^ůĞĞƉ Ĺ?Ć?Ĺ˝ĆŒÄšÄžĆŒĆ? x ,ĞĂĚ /ĹśĹŠĆľĆŒÇ‡ÍŹ ŽŜÄ?ĆľĆ?Ć?Ĺ?ŽŜ

x Neck & Back Pain x Arm & Leg Pain x Movement Disorders x Neuromuscular Disease x DĆľĆ?Ä?ĆľĹŻÄ‚ĆŒ LJĆ?ĆšĆŒĹ˝Ć‰ĹšÇ‡ x Ä‚ĆŒĆ‰Ä‚ĹŻ dƾŜŜĞů ^Ç‡ĹśÄšĆŒĹ˝ĹľÄž x And other Neurological Disorders

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The Journal of the Twin Cities Medical Society

November/December 2018

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Advances in Neurology Chronic Effects of Neurotrauma (Continued from page 19)

in 2006 conducted a review of literature determining the best time to provide nutritional support to patients suffering from TBI.1After reviewing 11 trials consisting of a total of 284 patients, the authors determined that early feeding is associated with the best long-term outcome. Immediate nutritional support was also found to be the most correlated with the reduction of symptoms that proved most debilitating on a life-long scale. Aiming to build off of this review, a Switzerland-based research team published a study in 2008 in the journal Critical Care to specify a nutritional protocol.2 They found that the best outcome for their 228-patient cohort suffering from severe TBI was when their glucose levels were closely managed for the first two weeks post-injury.

Many other pharmaceutical, psychologic, and lifestyle factors have begun to show promise as well. Dr. Ali Weinstein and colleagues at the Center for the Study of Chronic Illness and Disability investigated some of these other methods of reducing ailments associated with long-term TBI, specifically exercise.3 In 2017, this Virginia-based research team conducted a study to determine how aerobic exercise affected 10 patients suffering from long-term TBI symptoms. Results showed that both short- and long-term mood, following the exercise sessions, improved. Significant results were found only four weeks after beginning the exercise sessions. Promising research is currently underway which will inevitably continue to add tools that medical professionals can use to help TBI patients achieve the best recovery possible.

Impact Factors on Management

While the innovations in TBI management described above are directed toward the care for all patients, evidence has shown there are certain individualistic factors that play a role in the development 20

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of long-term symptoms in certain demographic groups. Senathi-Raja and her colleagues at an Australia-based research team published a paper in 2010 that examined the impact of age on long-term cognitive function of TBI patients.4 They discovered that patients who are older in age when succumbing to TBI are more likely to experience long-term TBI symptoms and have lesser cognitive ability. This trend may be due to resiliency characteristics observed from younger individuals upon injury.

Genetic factors also play a role in the predisposition for chronic effects in TBI patients. The most common genetic mutation associated with this higher risk for long-term TBI symptoms is arguably the apolipoprotein E (APOE) genotype.

The identification of this protein and its effects on vulnerability for chronic effects was demonstrated by Barry Jordan and colleagues.5 While evaluating the 30 boxers recruited in the study, Dr. Jordan found that those who were carriers of the APOE epsilon4 allele were more likely to experience increased chronic neurological deficits in his study population. This finding was further investigated in a 2018 study by Victoria Merritt and colleagues.6 Dr. Merritt determined the effect of the epsilon4 mutation on the neuropsychological performance of 53 TBI and 46 control military veterans. The results of her study were published in the Journal of Clinical and Experimental Neuropsychology and showed an association between the apolipoprotein genotype and reduced memory and overall cognitive speed and performance.

Summary

Brain injury results in complex pathophysiologic changes which require multimodal assessment. Patients with brain injury have diverse clinical symptoms and not all clinical symptoms have the same underlying pathophysiology. Prevention of the chronic effects of neurotrauma relies on successful identification and treatment of the acute effects of brain injury.

Neurosurgeon Uzma Samadani, MD, PhD, is the Rockswold Kaplan Endowed Chair for Traumatic Brain Injury Research at Hennepin Healthcare, and an Associate Professor of Neurosurgery at the University of Minnesota.

She can be reached at: Uzma.samadani@ hcmed.org.

Mohit Uppal is a senior studying Neuroscience at the University of Minnesota. He is currently an undergraduate researcher in the Brain Injury Research Lab, headed by neurosurgeon Uzma Samadani MD, PhD, at Hennepin Healthcare. In his upcoming years, he plans to pursue a Medical Degree and a Master’s of Business Administration.

References 1.

Perel, P., Yanagawa, T., Bunn, F., Roberts, I. G., Wentz, R., & Pierro, A. (2006). Nutritional support for head-injured patients. Cochrane Database of Systematic Reviews, (4), CD001530. https://doi.org/10.1002/14651858.CD001530. pub2.

2.

Meier, R., Bechir, M., Ludwig, S., Sommerfeld, J., Keel, M., Steiger, P.,…Stover, J. F. (2008).

Differential temporal profile of lowered blood glucose levels (3.5 - 6.5 mM versus 5 - 8 mM) in patients with severe traumatic brain injury. Critical Care, 12(4), R98. https://doi. org/10.1186/cc6974.

3.

Weinstein, A. A., Chin, L. M. K., Collins, J., Goel, D., Keyser, R. E., & Chan, L. (2017). Effect of Aerobic Exercise Training on Mood in People With Traumatic Brain Injury. Journal of Head Trauma Rehabilitation, 32(3), E49–E56. https:// doi.org/10.1097/HTR.0000000000000253.

4.

Senathi-Raja, D., Ponsford, J., & Schönberger, M. (2010). Impact of age on long-term cognitive function after traumatic brain injury.

Neuropsychology, 24(3), 336–344. https://doi. org/10.1037/a0018239.

5.

Jordan, B. D., Relkin, N. R., Ravdin, L. D., Jacobs, A. R., Bennett, A., & Gandy, S. (1997). Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing. JAMA, 278(2), 136–40. Retrieved from http://www.ncbi.nlm. nih.gov/pubmed/9214529.

6.

Merritt, V. C., Clark, A. L., Sorg, S. F., Evangelista, N. D., Werhane, M. L., Bondi, M. W.,…

Delano-Wood, L. (2018). Apolipoprotein E (APOE) 4 genotype is associated with reduced neuropsychological performance in military veterans with a history of mild traumatic brain injury. Journal of Clinical and Experimental Neuropsychology, 1–12. https://doi.org/10.10 80/13803395.2018.1508555.

MetroDoctors

The Journal of the Twin Cities Medical Society

Post-traumatic Stress Disorder Symptoms, Susceptibility and Treatment

A

s the Clinical Director at Vinland National Center, a Substance Use Disorder (SUD) treatment center for clients also suffering with traumatic brain injuries (TBIs) and other neurobehavioral disorders, we see a great deal of Post-traumatic Stress Disorder (PTSD) entering our program. Because it is estimated that one in two people suffering from SUD also suffer from a TBI, the associated trauma that must be actively dealt with can be signiďŹ cant in our line of work.

Post-traumatic Stress Disorder (PTSD) is a serious mental disorder that can develop after a dangerous or traumatic event. Clients experience recurring memories of the event; avoid situations, people or thoughts that remind them of the event; and experience altered mood and thinking patterns. Nearly 7% of people in the United States will suffer from PTSD at some point in their lifetime, according to the National Institute of Mental Health.

The four main symptom clusters of PTSD identiďŹ ed in the DSM-5 criteria are listed below: s )NTRUSION %XAMPLES INCLUDE NIGHTmares, unwanted thoughts of the traumatic events, ashbacks, and reacting to traumatic reminders with emotional distress or physiological reactivity. s !VOIDANCE %XAMPLES INCLUDE AVOIDing triggers for traumatic memories including places, conversations, or other reminders.

By Rick Krueger MA, LPCC, LADC, CBIS, and John E. Simon, MD

MetroDoctors

Rick Krueger MA, LPCC, LADC, CBIS

s

s

.EGATIVE ALTERATIONS IN COGNITIONS AND mood. Examples include distorted blame of self or others for the traumatic event, negative beliefs about oneself or the world, persistent negative emotions (e.g., fear, guilt, shame), feeling alienated, and constricted affect (e.g., inability to experience positive emotions). !LTERATIONS IN AROUSAL AND REACTIVIty. Examples include angry, reckless, or self-destructive behavior, sleep problems, concentration problems, increased startle response, and hypervigilance.

The Role of Genetics and Epigenetics

An article by Ryan, J. et al. on “Biological Underpinnings of Trauma and Post-traumatic Stress Disorder: Focusing on Genetics and Epigenetics� estimates the heritability of Post-traumatic Stress Disorder (PTSD) as 35%, but varies

The Journal of the Twin Cities Medical Society

John E. Simon, MD

widely when individual PTSD symptoms are examined. From the vantage point of genetics research, PTSD is considered a complex or polygenetic disorder. Unlike Huntington’s disease and other disorders that are caused by a single gene, there is likely no “PTSD geneâ€? that is necessary and sufďŹ cient for the development of the disorder. Instead, there are probably many different genes each of which contributes interchangeably and additively in a probabilistic fashion to the inherited liability for PTSD. More than 25 genes have been identiďŹ ed for their involvement in PTSD. The majority of genetic studies have been candidate genes, focusing on genes involved in neurotransmitter systems and stress signaling. Compared with other disorders, such as major depression, relatively few family studies of PTSD have been conducted.

(Continued on page 22)

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Advances in Neurology Post-traumatic Stress Disorder (Continued from page 21)

There are two main methods for conducting family studies: the family history method and the family study method.

Both methods begin by selecting cases and controls, which are called probands in genetic studies. The family history method collects psychiatric information about all family members by interviewing the proband. Moreover, most suggest familial psychopathology increases risk of both trauma exposure and PTSD, although the mechanism by which this occurs is unclear.

A family history of psychopathology could increase risk of PTSD directly or indirectly.

Brain Structures and Neurotransmitters

Bremner, J. D., in his article “Traumatic Stress: Effects on the Brain” identifies areas of the brain implicated in the stress response which include the amygdala, hippocampus, and prefrontal cortex. We know that stress can be associated with lasting changes in these brain areas. We have also learned that traumatic stress is associated with increased cortisol and norepinephrine responses to subsequent stressors. Cortisol at the time of a psychological trauma may facilitate overactivation of the central CRH-NE cascade, resulting in enhanced and prolonged stress responses. This increased stress responsiveness may be further accentuated by inadequate regulatory effects of GABA, serotonin, and NPY. Additionally, altered norepinephrine and stress hormone activity may be critically involved in processes of learning and extinction, both of which are abnormal in PTSD; for example, norepinephrine enhances the encoding of fear memories and glucocorticoids block the retrieval of emotional memories. The constellation of elevated noradrenergic activity and relative hypocortisolism may lead to the enhanced encoding of traumatic memories and the lack of inhibition of memory retrieval both of which presumably trigger re-experiencing phenomena in PTSD. Therapy and Treatments

In the article “Post-traumatic Stress 22

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Disorder: Management and Treatment” the Cleveland Clinic reports that Cognitive-behavioral treatments, either individually or in a group format, are regarded as the most effective treatment for PTSD. These therapeutic approaches include: s 0ROLONGED EXPOSURE This therapy is for treatment of individuals who experienced trauma fear and avoid the thoughts, feelings, and situations that remind them of it. The goal of exposure therapy is to eventually have less fear about your memories, and to learn to control their thoughts and feelings about the traumatic event.

Prolonged exposure is a specific therapy that includes four components: education about PTSD and treatment; breathing retraining to help manage anxiety; practice with approaching real-life situations that are related to the trauma; and, talking through the trauma experience. s

#OGNITIVE 0ROCESSING 4HERAPY This therapy helps with managing upsetting thoughts and feelings, and helps individuals with gaining a better understanding of the trauma and its effects. Therapy steps include: education about PTSD and treatment; monitoring thoughts and feelings, and understanding how the traumatic event altered views of one’s self, others, and the world; developing skills to change dysfunctional thoughts or “stuck points;” and, shifting beliefs affected by the trauma, such as safety, trust in one’s self and others, and self-esteem.

s

#OGNITIVE RESTRUCTURING THERAPY This therapy approach helps individuals identify and transform dysfunctional thought patterns and beliefs related to the trauma experience. The treatment utilizes daily diaries to track thoughts and feelings. With the help of a doctor, clients can learn to replace those thoughts with more accurate and less upsetting thoughts. A doctor will also teach the client ways to cope with feelings such as anger, guilt, and fear.

As clients learn how to recognize and

change their perceptions about the trauma, symptoms often improve. s

%YE MOVEMENT DESENSITIZATION AND reprocessing: Eye movement desensitization and reprocessing is a treatment that includes components of exposure and cognitive therapies. The idea is to use the brain’s information processing to resolve trauma reactions.

Treatment sessions involve thinking about the trauma, identifying negative trauma-related thoughts, generating positive aspects, and engaging in rapid side-to-side eye movements while focusing on the target trauma. Sounds, tapping, and other methods that activate stimulation of both halves of the brain have proven equally effective and are routinely used.

Medications

The National Center for PTSD describes medications used for PTSD and how the brains of those with PTSD process “threats” differently, in part because the balance of chemicals called neurotransmitters are out of balance. These clients have an easily triggered “fight or flight” response, which is what makes them jumpy and on-edge. Constantly trying to shut that response down could lead to the individual feeling emotionally cold and removed. Medications can help one to stop thinking about and reacting to what happened, including having nightmares and flashbacks. Medications can also help clients to have a more positive outlook on life and feel more “normal” again.

Several types of drugs affect the chemistry in one’s brain related to fear and anxiety. Physicans will usually start with medications that affect the neurotransmitters serotonin or norepinephrine (SSRIs and SNRIs), including: Fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft) and Venlafaxine (Effexor). The FDA has approved only Paroxetine and Sertraline for treating PTSD. Because people respond differently to medications, and not everyone’s PTSD is the same, a physican may prescribe other medicines

MetroDoctors

(Continued on page 24)

The Journal of the Twin Cities Medical Society

Haitham M. Hussein, MD, MSc, FAHA Medical Director, Regions Hospital Stroke Center

It’s about time When every second counts, families know they can depend on HealthPartners and Regions Hospital. Our stroke experts are connected by a common goal – getting patients back to their lives as quickly and safely as possible.

Regions Hospital is Minnesota’s first Comprehensive Stroke Center certified by the Joint Commission. We’re also recognized by Healthgrades® as a Five-Star Recipient for Treatment of Stroke for 8 Years in a Row (2011-2018).

Advances in Neurology Post-traumatic Stress Disorder (Continued from page 22)

“off label,” too. (That means the manufacturer has not requested the FDA to review studies of the drug showing that it’s effective specifically for PTSD.) These medications may include: Antidepressants, Monoamine oxidase inhibitors (MAOIs), Antipsychotics or second generation antipsychotics (SGAs), Beta-blockers, Benzodiazepines, and Alpha Blockers.

Vinland National Center’s Approach

At Vinland National Center the link between SUDs and PTSD shows that female substance abusers, in particular, have higher rates of this dual diagnosis (30% to 59%), most commonly deriving from a history of repetitive childhood physical and/or sexual assault. Rates for males are two to three times lower and typically stem from combat or crime trauma. Vinland Center has a Rule 29 clinic that provides assessments and individual cognitive therapy, and utilizes the Community Connections Trauma Recovery and Empowerment Model (TREM) for group therapy, which focuses on building skills around trauma. Additionally, the groups focus on lowering responses to trauma triggers and helping the clients to gain support utilizing culturally-related exercises and gender-specific approaches.

Clients attend group activities focusing on mindfulness, yoga, stress management and music, and meet weekly with psychiatry staff for evaluation of their mental health symptoms and medications management.

Our psychiatric approach includes the use of Alpha Blockers to reduce the PTSD symptom clusters of intrusive events and alterations in arousal and reactivity.

Our overall approach is based upon these Core Principles of a Trauma-Informed System of Care: s Safety: Ensuring physical and emotional safety s Trustworthiness: Maximizing trustworthiness, making tasks clear, and maintaining appropriate boundaries 24

November/December 2018

s

Choice: Prioritizing consumer choice and control s Collaboration: Maximizing collaboration and sharing of power with consumers s Empowerment: Prioritizing consumer empowerment and skill-building Additionally, Vinland Center applies universal precautions with staff assuming all clients have some kind of trauma history. They conduct a formalized trauma assessment; inform staff of confirmed trauma history and develop specific treatment plan interventions related to such. Dignity and respect should always be emphasized (Resident Rights and Respect Policy).

Vinland Centers clients with TBI present additional issues relating to attention, focus and the retention of information. These deficits are reduced by more frequent individual sessions, slower paced and repetitive interventions and education in PTSD and TBI. Overall, we have learned that one size does not fit all when it comes to both TBIs and PTSD. What works for one client may not work at all for another. Individualized care is where we have been able to have the most success for and with our clients. The greater the number of choices we have in combatting PTSD, the greater success our clients show in the end.

Rick Krueger MA, LPCC, LADC, CBIS, is the Clinical Director at Vinland National Center. He has worked in the area of behavioral health for over 25 years. He has presented trainings addressing co-occurring disorders, cognitive disabilities, building resiliency, and trauma-informed services internationally, nationally, and at the state conference level. Rick earned his Master’s Degree in Clinical Psychology at Loras College in Iowa. Mr. Krueger can be reached at rkrueger@vinlandcenter.org, or (763) 479-3555.

John E. Simon, MD is an adult and geriatric psychiatrist practicing in Minneapolis. He is board certified in Psychiatry, and specializes in Addiction and Geriatric Psychiatry.

Dr. Simon received his Doctor of Medicine Degree from the University of Nebraska, and completed a Psychiatric Residency at

the University of Minnesota Hospitals. He holds the title of Adjunct Associate Professor from the University of MN Department of Psychiatry. He is the founder of Creative Psychopharmacology in Minneapolis and consults to Vinland National Center.

References 1.

American Psychiatric Association. (2013).

Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.

2.

Bremner, J. D. (2006). Traumatic stress: effects on the brain. Dialogues in Clinical Neuroscience, 8(4), 445–461.

3.

Koenen, Karestan C., Harley Rebecca, Lyons Michael, Wolfe Jessica, Simpson John, Golberg Jack, Eisen Seth, Tsuang Ming, A twin registry study of familial and individual risk factor for trauma exposure and Post-traumatic Stress Disorder The Journal of Nervous and Mental Disease: April 2002 - Volume 190 - Issue 4 - p 209-218.

4.

“Post-traumatic Stress Disorder.” Cleveland Clinic (2015, March 3): Post-traumatic Stress Disorder: Management and Treatment Retrieved August 29, 2018 from https://my.clevelandclinic.org/health/diseases/9545-post-traumatic-stress-disorder-ptsd/ management-and-treatment.

5.

Men’s Trauma Recovery and Empowerment Model (M-TREM): A Clinician’s Guide for Working with Male Survivors in Groups Community (2012, March) Connections, Washington DC. Retrieved August 29, 2018 http://www.communityconnectionsdc.org/training-and-store/ store#!/Mens-Trauma-Recovery-and-Empowerment-Model-M-TREM-A-CliniciansGuide-for-Working-with-Male-Survivors-inGroups/p/80215961/category=22725096.

6.

Fallot, Roger D, Harris, Maxine, National Council for Community Behavioral Healthcare,(2011, Issue 2) Culture Shock. Retrieved August 29, 2018 https://www.thenationalcouncil.org/?api&do=attachment&name=trauma.

7.

Ryan, J., Chaudieu, I., Ancelin, M-L., & Saffery, R. (2016). Biological underpinnings of trauma and Post-traumatic Stress Disorder: Focusing on genetics and epigenetics. Epigenomics, 8(11), 1553-1569. DOI: 10.2217/epi-2016-0083.

8.

University Medical Center. (2017, July 11).

Imaging reveals how well PTSD patients will respond to psychotherapy, researchers find. ScienceDaily. Retrieved August 29, 2018 from www.sciencedaily.com/releases/2017/07/170711141402.htm.

9.

Veteran’s Administration Health Care PTSD: National Center for PTSD (2017, December 7).

Medications for PTSD, Retrieved August 29, 2018 from https://www.ptsd.va.gov/public/ treatment/therapy-med/medications-for-ptsd. asp.

10. Ryan, J., Chaudieu, I., Ancelin, M-L., & Saffery, R. (2016). Biological underpinnings of trauma and Post-traumatic Stress Disorder: Focusing on genetics and epigenetics. Epigenomics, 8(11), 1553-1569. DOI: 10.2217/epi-2016-00.

MetroDoctors

The Journal of the Twin Cities Medical Society

The Pleasure Reward System

L

ike it or not…it is the pleasure reward system that makes the determination, for not only human beings but all mammals, as to how we feel on a moment-to-moment basis.

Since the early 1950s, a lot of research has been put into the study of neurobiology. A lot of graduate students got their PhDs based on research in various university laboratories throughout the country.

So here we are today, the beneficiaries of over 65 years of elegant neural research.

So what do we know?

We know a lot. In 1987 two researchers, Doctors Roy Weise and Mike Bozarth, struck pay dirt when they inserted a neural probe into the midbrain region of a rat brain. What they discovered was then called the mesolimbic bundle. It is a region that sits at the top of the brainstem between two specialized islands of brain tissue, the ventral tegmental area (VTA) and the nucleus accumbens (NA). These two areas communicate with each other using the neurotransmitter dopamine. The levels of dopamine that are produced by various stimuli create how all of us feel on a moment-to-moment basis…our hedonic tone. This hedonic tone and the dopamine that creates it make our survival as a species possible. Serotonin in contrast influences how we feel over days or weeks. There is no involvement of serotonin in the fast acting pleasure reward system.

Stepping back a moment, this pleasure reward region was initially called the medal forebrain bundle. Problem was that the name did not mean much to non-neuroscientists. So a move was made to rename this important region to something

By Jeffery Morgan, MD

MetroDoctors

everyone would recognize — mesolimbic dopaminergic tract. This name change created even more confusion until a few decades back when it started to become known as the pleasure reward center.

The neural probes used in the rat and monkey studies showed that our dopamine levels come in four strengths. If there is a 100% amount of dopamine in the pleasure reward region, then we feel normal. If there is a only 50% then we feel dysphoric. Zero percent, that is to say no dopamine present, will result in a feeling of anhedonia, essentially numb emotionally. Now if the dopamine level is at 200% then the feeling produced is euphoria. So what?

Researchers found that if a friendly rat was put in a cage next to a monitored rat, the monitored rat’s dopamine level went from 100% to 125%. This was the result of positive social interaction. Give a monitored rhesus monkey a piece of chocolate and that monkey’s dopamine level will go from 100% to 150%. Thus, eating good food makes a positive change in hedonic tone. An orgasm will get the dopamine level from 100% up to 225%. Most people would likely agree that this is a euphoric feeling. But the positive reward that is felt is from Mother Nature wanting babies to be made and the species to continue.

The importance of the pleasure reward center is that every drug of abuse (with the exception of LSD which affects serotonin in a different area of the brain) hits this circuit with the efficiency of a hijacker getting into the cockpit of a plane and holding a gun to the pilot’s head. As you may imagine that plane is no longer going to go where the pilot wants. Alcohol intoxication will boost the dopamine level to 300%, heroin will get it to 450%

The Journal of the Twin Cities Medical Society

and methamphetamine can get it to an astounding 1,000%! As an aside, THC will get one to 175%. So when people say they don’t get high with marijuana they actually don’t. Euphoria, the feeling of “high” occurs at dopamine levels over 200%. Since we, or any animal, only do something if it makes us feel good or better it is easy to see how powerful over drivers of dopamine like drugs or alcohol can take over. Positive social interaction, eating good food and making babies are what keeps individuals, and thus the species, surviving not intoxicating mood altering drugs.

It is important to bear in mind that what goes on in the pleasure reward region of the midbrain is unconscious, unless it is communicated to the conscious part of the brain, the prefrontal cortex. The signal sent from the pleasure reward center will take one of three basic forms. The first: “I don’t know what you just did, but we must never do that again.” Good examples of this would be putting your hand on a hot stove, closing your hand in a car door or opiate, alcohol or benzodiazepine withdrawal. The second signal that is sent is: “I don’t know (Continued on page 26)

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Advances in Neurology The Pleasure Reward System (Continued from page 25)

what you just did, but we have got to do a lot more of that.” Examples of this would be having positive social interactions, eating a good meal with the family, having a healthy sexual relationship with a partner or getting high with oral opiates or heroin.

Finally, the third signal, only identified a few years ago, is called the expectation of reward. That’s a craving. Let’s say you are

really hungry and you walk into a homey kitchen and smell chocolate chip cookies baking. Your mouth starts to water and your stomach rumbles in anticipation of eating some delicious, warm fresh baked cookies. This is also the sort of feeling a patient with opiate use disorder experiences with the anticipation of seeing their dealer or using their drug of choice.

In the early 1990s many critics looked askance at this pleasure reward research on

THE SCHUSTER CLINIC FOR FOR ENDOCRINE FO END NDOC OC OCRI CRIINE N AND AND N METABOLIC MET ETAB ETAB ABO ABOL OLIC OL LIC C DISORDERS DISORDERS SO S −and− −an and d−

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rats and monkeys. They claimed it could not be applied to human beings. Perhaps they had a point, that is until about 1998 and going into the early 2000s. That is when positron emission technology (PET scans) started being used by Dr. Nora Volkow at the National Institute of Drug Abuse (NIDA). PET scans can monitor dopamine levels in the human brain. No neural probes required. And her results, and the research results of others, confirmed the validity of the earlier rat and monkey studies.

Illicit drugs and alcohol hit the pleasure reward center really hard. The brain attempts to compensate by striving to keep the dopamine levels normal by the neuroplasticity process of down regulation. To the individual with active substance use disorder (SUD), the now politically correct term for addiction, this feels like tolerance developing. Chasing the initial “high,” and the continual need to use higher drug levels are sought until tragically, and all too frequently, a fatal overdose occurs.

The take home message is that the pleasure reward system operates in every human being and animal. It aids our survival. But mood altering drugs and alcohol can hijack this system, creating the chronic brain disease of substance use disorder.

Let me repeat, addiction is not a moral weakness, or due to lack of will power, it is a chronic brain disease. It is an illness researched and identified after over 65 years of intense elegant research. It can be treated like any chronic illness. And as an old professor of mine once said: “The secret of a long life is to have a chronic illness and take good care of it.”

Jeffery Morgan, MD is residency trained in family medicine. He has been board certified and a fellow in both family medicine and emergency medicine. Since 2004 Dr. Morgan has been practicing full-time Addiction Medicine in St. Louis Park, Minnesota. He is board certified by The American Board of Addiction Medicine and is also a certified Medical Review Officer. Dr. Morgan is a strong advocate for individuals with substance use disorders, especially when complicated by co-occurring disorders. He is active in lecturing and addiction education.

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MetroDoctors

The Journal of the Twin Cities Medical Society

Environmental Health — Environmental Neurology

T

here are neurological syndromes associated with specific environmental toxins. These include lead encephalopathy, Parkinsonism (manganese exposure), nitrous oxide myelopathy, alcoholic cerebellar degeneration, etc. These disorders could be identified by careful observation because of the tight correlation between a single toxin, a relatively select population and a distinctive clinical presentation.

Identifying the neurologic consequences of complex toxic exposures is more challenging. Reasons include: a) the number of new and existing environmental toxins has multiplied exponentially; b) synergistic effects of multiple toxins are likely; c) exposed populations are large and heterogenous; and d) rather than causing distinctive syndromes these toxins increase the risks of common chronic disorders that among other things affect the nervous system (NS). Identification of toxic effects now requires complex epidemiologic investigations.1 Despite these challenges, a substantial body of research links many NS disorders to environmental conditions, particularly products of fossil fuel (FF) combustion including microparticulates, volatile organic compounds, and aerosolized heavy metals. Significant correlations have been demonstrated between exposure to these toxins and increased risks of cognitive decline and dementia, cerebral atrophy, neurodegenerative disorders, stroke, CNS malignancies, and developmental delay.

Airborne microparticulates released in

By Bruce D. Snyder, MD, FAAN©

MetroDoctors

wildfires and emissions from power plants and motor vehicle emissions can enter the circulation and have been identified in a variety of tissues including the brain. In addition, Greenhouse Gas (GHG) emissions create hotter conditions that in turn increase ozone concentrations (raising the risks of CVD and cancer) and heat-related illnesses including heat stroke.

The release of vast amounts of environmental toxins into the air and water constitutes a negative social determinant of health. Fortunately there are many effective measures physicians can take to help reduce their patient risk. For example, physicians can advise patients that eating less meat and doing more biking and walking are healthier (and better for the environment). Inquiries regarding lifestyle can be revealing: occupational exposures; living/working near highways or industrial sources of pollution, etc. We can counsel that when air quality is down stay indoors, exercise less (i.e. breathe less), consider a mask, etc. Shelter from extreme heat.

Realistically, however, our patients often have little control of exposure factors.

Beyond that, doctors can be leaders in reducing the pollution harming our patients and communities. Start by getting your clinics and hospitals to adopt clean energy and sustainable practices2 — after all, the U.S. healthcare sector is responsible for about 10% of GHG emissions and billions of tons of toxic waste annually.

Learn more at HealthCare Without Harm (https://noharm-uscanada.org).

Healthcare organizations have an important role to play in the development of

The Journal of the Twin Cities Medical Society

public policy. Here in Minnesota, organized medicine has successfully advocated for tobacco cessation and end-of-life choices. Can we take a more active role in advancing measures to reduce the pollution that is harming our patients, our communities, our children and ourselves?

References: 1.

Epidemiological Research on Adverse Neurological Effects of Exposure to Ambient Air Pollution. Xu et al. Front. Public Health 4:157. doi: 10.3389/fpubh.2016.00157.

2.

Greening Up Health Care. MetroDoctors 20 (2), March/April 2018.

ADULTS WITH

MILD COGNITIVE IMPAIRMENT NEEDED FOR STUDY If you have mild cognitive impairment and are 65 years of age or older, you may be able to take part in an exercise and cognitive training study. A specialist will work with you for 6 months. Compensation and gym membership provided.

Call 612-626-9490 to learn more Sponsored by the National Institute on Aging

November/December 2018

27

Dr. Pete Dehnel Public Health Advocacy Fellowship Launches This past September, TCMS launched the inaugural year of the Dr. Pete Dehnel Public Health Advocacy Fellowship. The fellowship offers opportunities for medical students to engage in local public health advocacy activities and creates a connection between medicine and public health for physicians-to-be at this critical time during their training.

The 11 students have each selected a topic to work on, including LGBTQ health equity, healthy food access, and housing as medicine, and have been paired with a physician mentor with experience in their area of interest. The following physicians have generously volunteered

the students will showcase their advocacy their time to mentor students during the work. Learn more at www.panmn.org/ coming academic year: fellowship.

Courtney Baechler, MD Pete Dehnel, MD Angela Goepferd, MD Matt Kruse, MD Lisa Mattson, MD Travis Olives, MD Eva Pesch, MD Danielle Robertshaw, MD Rebecca Thoman, MD Sarah Traxler, MD William Walsh, MD Please watch for an announcement for our closing 2018 Public Health Advocacy Fellows. reception in May 2019 where

HPV Vaccine It's about CANCER prevention.

Contact us to increase HPV vaccination rates at your clinic.

MAFP.ORG/HPV

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November/December 2018

MetroDoctors

The Journal of the Twin Cities Medical Society

Senior Physicians Association Holds Fall Meeting Physicians from throughout the metro area gathered on September 18, 2018 for the fall meeting of the Senior Physicians Association. Eileen Weber, JD, DPN, BSN, RN, Chair, Healthcare Legal Partnerships and Lindy Yokanovich, Esq., Executive Director, Cancer Legal Line, teamed up for a presentation on “Advancing Health Equity.” They showcased an innovative program that supports patient health by connecting them with legal services. Several local clinics have opened their doors to house this program onsite. Additional locations are being sought.

Mark your calendar for the upcoming 2019 events to be held on Tuesday, January 15 and Tuesday, May 21; invitations will be sent to all TCMS physicians via email. Contact Nancy Bauer at (612) 623-2893; nbauer@metrodoctors.com for more information.

In Memoriam ELLEN BUCHANAN, MD, passed away on July 11, 2018. Dr. Buchanan was a psychiatrist, specializing in Addiction Medicine, at the University of Minnesota. She joined the medical society in 2007.

TERRANCE CAPISTRANT, MD, passed away on August 24, 2018. Dr. Capistrant was a founding partner of Neurologic Associates of St. Paul. He joined the medical society in 1971.

ANTON “TONY” SPRAITZ, MD, passed away on September 16, 2018. Dr. Spraitz co-founded St. Paul OB-GYN in 1963 and is a past-president of the St. Paul Surgical Society. He has been a member of the medical society since 1962. *!.%44% 342!4(9 -$ passed away on July 28, 2018. Dr. Strathy was an OB/GYN, practicing at Park Nicollet. She held many leadership positions including Chair, Park Nicollet Board of Governors, and Vice Chair, American College of Obstetrics and Gynecology. Dr. Strathy was recognized by MetroDoctors as a Luminary of Twin Cities Medicine in 2016. She joined the medical society in 2009.

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The Journal of the Twin Cities Medical Society

November/December 2018

29

CAREER OPPORTUNITIES

See Additional Career Opportunities on page 31.

Join the Best.

Join Entira Family Clinics.

Entira Family Clinics is an award-winning, physician owned and operated group of primary care, after hours care, and express care clinics serving the East Metro for over 50 years. If you want the opportunity to influence how your practice is run, then look no further.

Where Generations Thrive®: Our community-based clinics offer high-quality care specializing in family medicine and serve families at all stages of life.

Join our team today!

For more information, contact: Len Kaiser: 651-772-1572 or lkaiser@entirafamilyclinics.com

| entirafamilyclinics.com | | 30

November/December 2018

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MetroDoctors ½ page 0918 1817236

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CAREER OPPORTUNITIES

Please also visit www.metrodoctors.com

Recruit With

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Join our family of physicians.

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Call 1-800-842-6469 Email recruit1@fairview.org Visit fairview.org/careers Physician Opportunities: Cardiology (Electrophysiology)

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With just one click you will ďŹ nd information on the latest TCMS and &OUNDATION NEWS current and past issues of MetroDoctors; and new career opportunities!

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November/December 2018

31

LUMINARY of Twin Cities Medicine

By Marvin S. Segal, MD

LYLE A. FRENCH, MD, PHD He was born in South Dakota and grew up in rural southwestern Minnesota, yet he played prominent roles in the exciting and storied historical pathway of Neurosurgery as a clinical specialty and the ongoing maturation of the U of M Medical School. Let’s see how this all came about.

Dr. Lyle French, after a pre-medical Macalester College education, received his BS, MB, and MD degrees at the U of M. His general surgery residency under Dr. Owen Wangensteen (Luminary 2011) and neurosurgical residency under Dr. William Peyton, were interrupted by U.S. Army medical service in the North African and European theaters of WW II. After completion of his formal residency and with a U of M faculty appointment in hand, MS and PhD degrees were conferred under the guidance of Dr. A.B. Baker (Luminary 2013).

His career blossomed as he attained the rank of Professor and then Director of Neurosurgery with its newly acquired departmental status. Dr. French, a tall, polished and distinguished figure in his crisp white coat, was an imposing presence striding through the halls of his hospital. In an interview, well before his 2004 death at the age of 89, he opined that his major contribution was “the teaching of medical students and residents” with its admirable secondary impact of “contributing to the future of medicine.”

In addition to being a fine lecturing and bedside teacher, he was a master surgeon who excelled in the resection of cerebral aneurysms and who developed an acclaimed technique for A-V malformation ablation. He hailed the development of stereotaxis, sophisticated diagnostic imaging and use of the operating microscope, as he stimulated the curiosity and creativity of those with whom he collaborated and trained in ultrasonic brain scanning and fundamental studies of the ultrastructure and treatment of cerebral edema.

Lyle was an acknowledged national and international leader.

As the president and/or chair of virtually every American neurosurgical organization (Neurosurgical Society of America, etc.), he also shared his remarkable fund of knowledge as Chairman of the Board of Editors of the prestigious Journal of Neurosurgery, the Advisory Council of the National Institutes of Health, and via numerous worldwide lectures. A remarkable number of Dr. French’s mentees became academic neurosurgical chiefs throughout the U.S. and around the globe. Dr. Ed Sjeleskog, a former resident of his, stated, “An important legacy of Lyle is the number of people he trained for academic neurosurgery.”

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Lyle French became the initial Vice President for Health Science Affairs, transitioning with a firm hand into meaningful administrative activities at our U of M — there guiding his present and future colleagues into the medical world of standardized reporting and a burgeoning emphasis on quality of care and the cost/ value equation. During the medical school’s growth and building program, he dealt effectively and fearlessly with the state legislature and federal bureaucracy to reach architecturally attractive and practically sound structures that remain professionally employed and enjoyed today.

The French family home was an open and frequent site for Lyle, his wife Gene and their three children to informally entertain his residents, colleagues and a bevy of family friends. And... the good doctor’s non-professional activities — early on as an accomplished college basketball player and later as a devotee of golf and the out-of-doors pursuits of hunting and fishing — were solid evidence of his well-rounded persona.

So, along the way from the ancient and early crude activities of neurosurgery, such as trephination and nerve conduction function, to today’s intricate technologically assisted microsurgical techniques — Lyle French was there! When life threatening cerebral edema or an aneurysmal hemorrhage developed — Lyle French was there! And when his alma mater needed a proficient mentor or a skillful administrator — Lyle French was there!

We heartily salute the many contributions of our outstanding Luminary.

This last page series is intended to honor esteemed colleagues who have contributed significantly to Twin Cities medicine.

Please forward names of physicians you would like considered for this recognition to Nancy Bauer, Managing Editor, nbauer@metrodoctors.com.

MetroDoctors

The Journal of the Twin Cities Medical Society

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