Hi,
I came across this website friday 29th June 2012. I have been researching for around two years now in regards to what could be the cause of my sons sudden pain in his cheek and forehead. My son is called riley, around the age of two riley started with funny episodes where he would get facial pain in his cheek and head. This made him sick on several occasions, he would also sleep for sometime after the episodes.
Riley has been under his paediatrician since they started who thought possible seizures was the cause. Riley has had EEG, ECH metabolic blood tests and urine samples. All were reported as satisfactory. Riley's last appointment was on Monday 11th June 2012 which his paediatrician left us with no answers and asked us just to keep my son off his wii and see how he goes. He was also discharged, so we was still left in the dark. On Friday 29th of June riley woke crying in pain around 11pm we gave him paracetamol. He cried for around 30-40 minutes, in pain holding his cheek.
Asked me "mum why does this keep happening to me" his voice desperate for answers. Riley was 5 in January, this has gone on for some time now and we are still left with no answers. Having to explain to my 5 year old son that I don't know is just not the answer. I sat frantically trying to research Riley's symptoms on the Friday night. I came across this site where I found a story called Emily's story. Emily's story sounds exactly the same as Riley's.
Riley's and Emily's symptoms are very much the same. I have now written to my sons paediatrician with details so hopefully they can look into TN, I would appreciate any information or advice you can give me. I'm desperate for some answers as I can't stand seeing my son like this any longer.
Thank you for taking your time to read my email.
Why Is Research
Important
By Kenneth Casey M.D., FACS
Clinical Associate Professor of Surgery (Neurosurgery) Michigan State University SOM
Clinical Associate Professor of PM&R Wayne State University SOM
Surgical Director Intensive Care Oakwood Southshore
Have you ever gotten up in the morning and been very excited about the prospects for the day? You’ve have a new friend to meet or you’re going on a trip to an area you’ve never been or you’re going to revisit and reconnect with an old friend. All these are exciting because something new is going to happen, something different, and you’re going to come away with new feelings and different perspectives. Research is exactly like that. The origin of the word from the old French says exactly that, that you’re going to look very intensively for something( Old Fr. recherche).
Researchers get involved because they get excited about something that’s not known or something that’s not completely explained and they dedicate literally years of their lives, days of their weeks, and hours of their days trying to find these bits of information. What’s even more fun for a researcher though, is finding other pieces of information, little sidebars as it were, that were not known before. These sidebars are important ,not as a detour, but as an increasing amount of knowledge that’s adding to the general fund of things we know and things we can work with in our lives. People talk about the fact that research is important in medicine because it makes it possible for some cures or some improved treatments and that’s certainly the case with the Facial Pain Research Foundation. It means much more than that because if we can find how something works, whether it be something in our own body or something outside our body in the atmosphere or something outside ourselves beyond the planet, we’re going to be that much richer for the experience. We also know that research allows us to understand several sides of a given question.
For years the world was flat and everyone believed you could sail off the end. Researchers and explorers showed that based on their calculations from the time of Galileo and da Vinci to the times of Columbus and other explorers that that’s not true. It is a circle of land, water, and people. The world exists as a collected community. Research can provide truth and put paid to certain mistruths or errors in knowledge that may hold us back and may stop us from going in the right directions. It’s a way to support day to day life and to support fundamental truth.
Research offers us all an opportunity to pursue more each day when we get up and when a researcher puts together a hypothesis and begins the steps to take that hypothesis piece by piece and develop it into a theory and the theory translates into practice, every single one of us will benefit.
Research is important because we go back and search again through what’s happened and look again at what has already been written down and done and with a very critical eye and an unparalleled intensity, we ask what more can we do, what more can we accomplish, what more can we learn.
Editors Note: Hanna Smith is a contributing writer for the Facial Pain Research Foundation. She is an award-winning journalist and assistant author of an in-progress medical biography detailing life with chronic pain. A student of bioclinical science, Smith studies surgical technology, psychology, physiology, and neurobiology to specialize in the medical treatment of individuals with disorders such as Trigeminal Neuralgia. Her father, diagnosed with Type-I TN for 26 years, inspired her to be dedicated to and engaged in the awareness, research, and medical practices that change the lives of people with chronic pain.
Shelly Forster:
The Purpose of Pain
Shelly with her family
By Hanna Smith
It was Shelly Forster’s most burning question: What is my purpose?
Fighting through reconciling the logistics of her new life diagnosed with chronic pain, rock bottom became her home in 2008 – and it left her with a choice.
2008 is the year Forster underwent two brain surgeries and was diagnosed with three chronic pain disorders – oral mandibular dystonia, trigeminal neuralgia and tardive dyskinesia – all of which transformed her from an independent woman working in nuclear engineering to a homebound patient fighting for her life.
“Pain is the great debilitator,” Forster said. “Chronic pain is a different animal all together, but takes on a new, terrifying element when it’s neurological.”
A congenital tumor inside Forster’s cerebellum was the root of her startling symptoms – muscular contractions in her neck, loss of voluntary control of her jaw and tongue, and splitting migraines.
For some time prior, Forster attributed the consistent headache and preliminary symptoms to stress at her job as a document control specialist for a nuclear engineering company. Such a job often required 70-hour weeks with round-the-clock hours. Forster assumed her symptoms to be somewhat normal considering the abnormal circumstances.
However, when the pain worsened and ultra-abnormal symptoms arose, she sought medical attention. Forster walked out of the doctor’s office with an emergency brain surgery scheduled the next day to remove the tumor inside around her cerebellum – the brain’s motor control center, which explained the involuntary movements in the cervical region of her head.
Dystonia impacts approximately 250,000 people in the United States, according to the American Association of Neurological Surgeons. Despite it being the third most common movement disorder, it is widely un-recognized by the public.
Forster underwent a surgery which removed the tumor. She was able to go home and began the recovery process. However, during a follow-up appointment, an additional MRI revealed there was a secondary tumor – this time woven within her cerebellum.
Forster for the second time was scheduled for emergency surgery, during which the surgeon filleted her cerebellum to remove as much of the tumor as possible. By the time the surgery was finished, however, 20 percent of the tumor was untouchable and too entangled in nerves. This portion still remains in Forster’s cerebellum to this day.
Prior to the operations, Forster says she understood her painful symptoms were in direct correlation with the tumors. Thus, following the surgical removal, she also assumed, based on medical opinion, that those symptoms would disappear.
Reality, however, did not meet those expectations.
Because of the neural damage coupled with the manipulation of the cerebellum during the procedures, Forster was left with permanent damage that resulted in her ongoing diagnosis of TN, dystonia, and tardive dyskinesia. It took visits to approximately four doctors before she was properly diagnosed.
THE FIRST THREE YEARS
With fluctuating medical treatments as doctors attempted to find a perfect medicinal cocktail to treat her pain – all the while attempting to acclimate to these new doses – Forster remembers the first three years of her illness as a fog.
During that time, she kept journals. Always a writer since childhood, putting her thoughts – no matter how jumbled – on paper helped her express and sort the emotions jostling through her mind.
“I took notes. I wrote things down about how I felt and what I was thinking – my faith and family and the roles both played,” she said. “I wrote down the good and the bad.”
Many days, Forster’s pain levels were off the charts and she was unable to function. It was during this time that she asked the pivotal question which determined the rest of her life: What’s my purpose?
Finding a purpose in the pain, she said, was the key for her survival by developing psychological motivation which would bolster her physical perseverance.
A wife, mother of three and now grandmother of three, Forster says she didn’t have to look far. Additionally, she began to recognize the unique position her illnesses put her in. Forster said this made her feel responsible for sharing her story with others – with the end goal of letting people with chronic pain know they’re not alone.
Fighting for her health meant fighting for her family and for others in similar situations.
Forster clearly found her purpose.
“It’s easy to accept your situation and move on,” she said. “But when you start paying attention to the battle and educate yourself, you’ll increase your quality of life.”
THE OTHER SIDE
Amid the turmoil of the first three years, a precedent was set in many facets of Forster’s life – experiences which developed the dynamics of what would become her new normal.
“I was able to discover trends,” she said. “I put a magnifying glass over the truth.”
Some relationships were lost. And although those years are met with what she says are some regrets, she knows the Shelly Forster of that time was often not reflective of her true character. During those times, pain sometimes spoke louder.
“It’s OK to walk away from relationships, no matter who they are, if that person cannot support them during their darkest moments,” she said. “We need to be relieved from that accountability.”
On the other hand, however, she says she knows the lost relationships proved who would stand by her side through the worst time of her life – and who couldn’t or wouldn’t. From that point, she established her core team of reliable people who became her baseline for support.
“When pain begins to define relationships, you are beginning to find out what other people are made of,” she said. “It’s the recognition that, because pain is part of my everyday life, those people are the ones that I need to walk away from for my benefit.”
Forster also established a core medical team. Because of the rarity of her disorders, she was referred to medical specialists, many of whom were considered cutting edge in their fields. But, being cutting edge, she discovered, did not equally entail compassion and willingness to advocate for patients. Through this realization, Forster learned to advocate for herself – even if it meant cutting off ties with doctors whom did not have her best interest in mind or were unwilling to help in her fight for her life.
This journey ultimately landed her at the Rochester, Minnesota-based Mayo Clinic, where she began undergoing botulinum toxin injections. According to The Dystonia Society, BTX treatment injects Botox directly into the targeted muscle which is impacted by dystonic activity. Although botulinum toxin is toxic in purified and controlled doses, it can help to relax muscular activity.
At the Mayo Clinic, Forster was treated by now-retired Dr. Joseph Matsumoto, who every three months typically administered 12 injections into her cervical muscles. The needles, approximately 30-gauge, are connected to a monitoring machine which judges the muscular-contraction activity at the time of injection with an auditory response. Always, the machine is buzzing at high volume when the needles are inserted. Forster’s husband Tom said sometimes he can see the needle bend slightly as it attempts to pierce the muscle.
Her daily companion for treatment is the pill box – containing pills assisting with pain relief, muscle relaxers, antispasmodics, blood pressure for hypertension linked to pain, and anti anxiety. Creating this fine-tuned cocktail took 10 years, and Forster said it still changes periodically as new medications are produced. It’s all trial and error.
NEW NORMAL
For all the absurdities and abnormalities in her life, Forster recognized trends and patterns – details that made her world a better environment. She learned her body’s unique responses to treatments or the lack thereof. Mitigating stress and being selective regarding which social interactions were most pertinent allowed her to venture from home without facing devastating impacts.
“What I’m going through is overwhelming enough,” Forster said. “I’m just getting through this moment. And not just get through. I’m trying to live this moment. Chronic pain patients need to know there’s life.”
Moving forward in this mindset, Forster said she’ll often plan ahead when she knows there is an important event she wants to attend – such as her grandson’s birthday party. In the days leading up to the event, Forster will rest more frequently and ensure she’s medicated properly.
Forster continued to write. This time, however, it was tracking her knowledge, medical progression, and jotting down pieces of inspiration that ignited fire in her fight for life. From psychology to medical management, Forster began to formulate her new normal.
At the same time, her purpose of pain began to grow arms and legs – and a plan came into focus. Forster fell back on her writing abilities, ultimately beginning work on a medical biography to share her story and gained knowledge to assist others who need direction in learning how to find a new normal after a chronic pain diagnosis.
Looking back, Forster recalls the many dark days when she considered what her purpose was. But, today, she is grateful to be alive with her purpose living and growing around her in the form of family and advocacy for others.
“The dark days behind me taught that the dark days to come are survivable,” she said. “Every time you have to apply that strength, it means you’ve got it in you for the next time.”
The Facial Pain Research Foundation
Board Of Trustees
Founding Trustees
Myron A. Hirsch, Ph.B., an author, editor and book publisher, founded Whitehall Printing Company (a book manufacturer) in 1959. The company prints thousands of books each year, including educational books on neuropathic facial pain for patients and their families, as well as health-care professionals. Hirsch also is editor-in-chief and publisher for Collage Books Inc. He is championing efforts to find a cure out of passionate concerns for his wife, Harriet, who experienced a return of trigeminal neuralgia in August 2010 after enjoying many pain-free years resulting from a Gamma Knife® procedure. He is a former president of the TNA-FPA, and was an active board member for 8 years. He and Harriet live in Naples Florida. Today Harriet is again pain-free.
Roger L. Levy, Esq., LLM, AIFA®, is a former attorney now serving as CEO of Cambridge Fiduciary Services LLC, a fiduciary consulting firm based in Scottsdale, AZ. Educated in England, he practiced law in London and was a partner in Taylor & Humbert, one of England’s oldest law firms, before immigrating to the United States in 1975 where he joined Saul Ewing Remick & Saul in Philadelphia. He holds a Master’s degree from Temple Law School.
Levy became an international spokesperson for the cause of trigeminal neuralgia for a compelling personal reason. For eight years, he suffered “in a wilderness of pain” that shut down his career and forced him into a dark corner of silence. When his pain was finally ended in 1997 through microvascular decompression surgery, he became an active volunteer with the TNA-FPA and Chairman of its Board from 2000 to 2013. He has continually championed the need to find a cure. He and his wife, Maddie, live in Scottsdale. Emeritus.
Michael Pasternak, Ph.D., an entrepreneur who co-founded the world’s largest retail hosiery company, started a Trigeminal Neuralgia Association support group in Nashville, Tenn. after suffering with trigeminal neuralgia. He later left the corporate world and became a board member and subsequently president of the TNA-FPA. He coordinated the association’s early national conferences for health professionals and patients, and helped it develop patient materials, support groups and a patient registry. Prior to his business career, he served as a professor at Vanderbilt University, the University of North Carolina and Michigan State University where he taught courses in Understanding and Improving Organizations and Leadership. Pasternak underwent successful microvascular decompression surgery for TN in 1992, and remains pain-free today. He and his wife, Sherrilyn, live in Gainesville Florida.
As a Founding Trustee of The Facial Pain Research Foundation Michael is focused full-time on the Foundation’s research, fund-raising, and organizational activities. Michael and his wife Sherrilyn enjoy their ten grandchildren, agility dogs, and travel.
Trustees
Douglas K. Anderson, Ph.D., Eminent scholar professor and chairman emeritus of neuroscience at the University Of Florida, College Of Medicine (UFCOM) and McKnight Brain Institute (MBI). As Director of Research of the Facial Pain Research Foundation (FPRF) Dr. Anderson has been responsible for setting the research priorities of the FPRF by selecting five diverse,
novel projects to fill out its research portfolio. Dr. Anderson is known for his pioneering laboratory research that led to the nation’s first implantation of human embryonic nerve tissue in eight patients with a specific complication of spinal cord injury in order to establish the safety and feasibility of nerve tissue transplantation in humans. Prior to his transplantation studies,
Dr. Anderson contributed significantly to the development of the first frontline medication for acute spinal cord injury. A graduate of Michigan State University, he was selected to be a senior research career scientist with the Department of Veterans Affairs in addition to serving 10 years as chairman of the Department of Neuroscience at the UFCOM and interim
executive director of the MBI for a year prior to his retirement. He and his wife, Beth, live in Gainesville, FL. and in Carmel, IN.
Richard Baron, Esq., since 1980, has been the managing principal of the Law Firm of Richard Baron & Associates. With almost 40 years of litigation experience in the Federal and State Courts throughout Florida, Mr. Baron has tried hundreds of cases dealing with commercial and transactional matters, family law matters, Florida Bar disciplinary matters, and criminal matters. Mr. Baron has been appointed numerous times as a Guardian Ad Litem to assist Family Court Judges in difficult cases with alcohol and drug issues and was honored by the Eleventh Judicial Circuit as the “Guardian ad Litem of the Year” in 2009. In addition, Mr. Baron has argued many cased before the Supreme Court of Florida. He has experienced the pain of trigeminal neuralgia and for many years was a Director of FPA-The Facial Pain Association.
Daniel P. DiCaro has extensive business experience as an executive in several public and private companies. With those companies, he has been a member of the Board of Directors and/or has been responsible in various roles for all aspects of executive level management including areas such as product and business development, finance and operations. He has a strong background in corporate finance, mergers and acquisitions, private equity and venture capital financing. He most recently served as an Operating Director of City Capital Advisors, an investment and merchant banking advisory firm starting in 2006 before stepping aside for health reasons in 2013. He has experienced trigeminal neuralgia and is passionate about providing the leadership necessary to find the cures and end the pain for everyone.
Suzanne N. Grenell, MBA, is a creative writer, poet, motivational speaker, and author of several inspirational books, including End The Pain; Neuropathic Facial Pain Expressions and Impressions. She became an active volunteer in helping others after suffering with trigeminal neuralgia for a dozen years, and overcoming two bouts with breast cancer. She is now pain-free, cancer-free and medicine-free. After earning a Master of Education degree at the University of Minnesota and an MBA at Arizona State, she taught high school social sciences for six years and served in worldwide positions with Intel Corporation for 23 years. She is a former member of the TNA-FPA Board of Directors, and lives in Scottsdale, AZ.
Elizabeth Cilker Smith is recently retired after 25 years at Cilker Orchards. There she served as Vice President assisting with the development of commercial, residential and office development in Silicon Valley, California. During that time she organized the Town of Los Gatos business Boulevard Community Alliance, served on the General Plan Committee, presided as President of Los Gatos Rotary and was a member of various nonprofit boards. After suffering from Trigeminal Neuralgia for 6 years she had a successful micro- vascular decompression surgery. Since then her passion is to help others so no one suffers the traumatic pain that afflicted her. She served as Secretary of Trigeminal Neuralgia Association and later became the West Coast Coordinator of FPRF.
Through her parents, she facilitated the donation of the William H. and Leila Cilker grant to the DNA Genetic Research Project. Elizabeth holds a MA in Education, serves on the Cilker Orchards Management Corporation Board, and the West Valley Community College Advisory Board for the Bill and Leila Cilker School of Art and Design.
Pat Tomasulo is the Sports Anchor and Reporter on the WGN Morning News. He joined WGN-TV in June 2005. Prior to coming to WGN-TV he was a Sports Reporter and Anchor in Buffalo, New York and in Rhinelander, Wisconsin. In August of 2009, Pat was voted one of the top five broadcasters chosen to sit alongside Kelly Ripa as co-host to “Live with Regis & Kelly” as part of a nationwide promotion. He was also one of the hosts of “Shaq Vs,” a nationally televised reality show featuring basketball superstar Shaquille O’Neal. Pat and Amy Tomasulo have raised over $1,200,000 at four “Laugh Your Face Off” comedy fund-raisers benefiting The Facial Pain Research Foundation at the Chicago Laugh Factory.100% of the proceeds were donated to The Facial Pain Research Foundation. Pat Tomasulo, the event's host and one of the scheduled comedic performers, has personal experience with the disease as his wife, Amy, has suffered from its devastating effects for years.
Jay Winer, independent marketing/public relations consultant and fund-raiser, formerly served as executive director of public relations and community affairs for The Grove Park Inn Resort and Spa in Asheville, N.C. He achieved over 50 national television specials and print featurestories as well as regional and local news coverage, resulting in over $15 million in advertising value equivalency. He worked with his wife, Maddy, to book popular entertainers and direct over 100 theatrical and concert stage events. He is a leading supporter of historical resources, National Historic Trust and the humane society in the Asheville area. Jay has provided volunteer services to the TNA-FPA for twelve years. Although not affected by facial pain, he gained compassion for people in pain when he heard their stories and talked with them while videotaping a series of national TNA conferences led by his friend, Michael Pasternak. Jay said he became hooked on the cause of finding a way to bring relief to men, women and children struggling with terrible pain. He and his wife, Maddy, have homes in Asheville and Indialantic, FL.
Former Trustees
Jean Raymond is retired after working over 25 years in computer programming, software design,
network architecture, database management and tracking systems. Jean has rendered technical support for
companies such as Western Electric, Digital Equipment Corp. and Dartmouth College/Dartmouth
Medical School. She has served on TNA-FPA Board of Directors since 2010. Jean was appointed
to the FPRF Board of Trustees to serve as liaison with the TNA-FPA board. She lives in Middlebury, VT.
Albert Rhoton, Jr. 1932-2016
World Neurosurgeon of the Year Albert Rhoton, Jr., MD., was a Facial Pain Research Foundation (FPRF) Trustee.
He had treated over 3,000 patients with trigeminal neuralgia and related neuropathic pain before he retired and became the inspiration for the FPRF’s cure research projects. His guidance and vision was evident when he proclaimed the founding of The Facial Pain Researth Foundaion was
“ONE OF THE MOST IMPORTANT DAYS IN THE HISTORY OF TRIGEMINAL NEURALGIA!”
In March, 2013 He said “it is time to find a cure!” and the Foundation’s
International Consortium of renowned scientists moved forward.
CODA Joins Facial Pain Research Foundation
International Scientific Consortium
By Michael Pasternak
I am excited to say on New Years Day 2018, The Facial Pain Research Foundation (FPRF) has six Foundation and two corporate funded scientific research projects actively working to find the cure for trigeminal neuralgia and related neuropathic pain. The scientists working on these projects are members of our International Scientific Research Consortium. In the past this World Famous WebNewspaper has printed numerous stories about the Foundation funded projects (see Dr. Douglas Andersons 2017 Report). In October, 2017 the FPRF announced that Neurona Inc. (a corporate funded research project joined the FPRF Scientific Consortium. Neurona is focused on the discovery and development of cell-based therapies to treat intractable neurological diseases including TN and related neuropathic pain. Today the Foundation is pleased to announce that CODA, another corporate funded scientific project, is joining the FPRF International Research Consortium.
CODA Biotherapeutics is a San Francisco based pre-clinical stage biotechnology company developing a novel therapeutic platform for the treatment of chronic pain and other severe neurological disorders. CODA’s innovative platform relies upon a gene therapy approach to modulating aberrant neural activity, which CODA’s co-founders -- a team of forward-thinking biotechnology entrepreneurs, scientists, and clinicians -- believe will provide relief to patients suffering from intractable neuropathic pain such as that associated with trigeminal neuralgia and establish a new treatment paradigm for severe neurological disorders. The entire CODA team enthusiastically welcomes the opportunity to join the Facial Pain Research Foundation’s Scientific Consortium in developing new treatment options for patients with trigeminal neuralgia.
Building upon the groundbreaking work of the company’s founders and Scientific Advisory Board members, several of whom have been associated with FPRF, CODA is using advanced synthetic biology approaches to engineer novel neurotransmitter receptors that respond selectively to non-addictive and non-opioid-based small molecules. These engineered neurotransmitter receptors are delivered to pain-signaling neurons using viral vectors by standard of care neurosurgical procedures. Hyperactive target neurons that express the receptor, including those in the trigeminal ganglia, can then be controllably silenced by oral administration of the safe small molecule. Because the treatment molecule exclusively activates the receptor, it is possible to achieve highly selective blockade of the critical pain signals from reaching the brain. This effectively opens the “therapeutic window”, reducing the potential for adverse side effects. Preclinical studies in multiple neuropathic pain models have demonstrated that this technology provides robust, durable, tunable, and reversible pain control, without the side effects experienced with existing small molecule therapies (e.g. opioids, anticonvulsants, tricyclic antidepressants) or neurosurgical procedures (e.g. ablation, neurostimulation implants). CODA anticipates that this technology will be used to manage intractable chronic pain across a multitude of conditions, including trigeminal neuralgia, and it will be applied broadly to other peripheral and central nervous system disorders in the future.
Genetics Study
Finds Genes That Cause Trigeminal Neuralgia
Introduction by Michael Pasternak
In 2012 The Facial Pain Research Foundation approved a research study to find the genes responsible for trigeminal neuralgia.
While each of our Foundation’s scientific projects are valuable, the one that has been the most awesome and challenging for me has been the Genetics/DNA project. Dr. Doug Anderson (FPRF Director of Research) and I have had to communicate with scientists from four different countries (including Joanna Zakrzewska in London) and Collection Centers in 9 different cities in three countries! Doug has spent months on this project “everyday”! He has also had to communicate with additional scientists interested in our efforts and has done this while still overseeing the creation and development and evaluation of all of our Foundation’s other projects! How did we and he get so lucky?
While Doug has overseen and worked through the science some of our other Volunteers have been involved in working with the DNA Collection Centers, working through intellectual property problems, legal questions, raising the funds to pay for all of this, communicating to patients to give their DNA, creating PR pieces for the public to participate, keeping track of collection numbers, certifying completion of collections and data sent to OHSU and Rutgers, and making payments to the Collection Centers for their efforts. This project has been an enormous accomplishment. No Volunteer Foundation or organization has ever done this before! All completed while we grew our outstanding scientific project numbers to six and linked with two venture capital funded research projects.
The FPRF has spent over $650,000 of funds raised by our Volunteers and donors on this project. The FPRF Trustees have committed another $325,000 to complete the project in the next year.
So, now we have a team of scientists who have worked hard using their unique skills and understandings and have presented a report to our Trustees and asked to go forward to replicate the study during the next year to prove that what they have found are really the genes that will lead us to finding the cures. The Cilker Genetics/DNA Research Report has arrived. It is remarkable. We are extremely thankful to Drs. Devor, Burchiel, Seltzer, Diehl and Anderson for all of their voluntary efforts to create these findings. We are also truly thankful for Our Trustees and all of our Volunteers who helped raise the necessary funds to complete the tasks. This is an exciting time for all of us committed to ending the pain for all TN and related neuropathic sufferers.
The Following is a Non-Technical Summary Report…The detailed full Scientific Report has been presented to the Foundation Trustees and contains confidential information. It will be confidential until the replication of findings has been completed. Following the report is an article by Dr. Scott Diehl for general distribution.
Genome-Wide Association Study
Of Trigeminal Neuralgia Type 1 (TN1)
The William A. and Leila A. Cilker
Research Project
A Report Prepared for the Board of Trustees of the Facial Pain Research Foundation by Kim J Burchiel, MD (Oregon Health and Science University), Marshall Devor, PhD (Hebrew University of Jerusalem), Scott R Diehl, PhD (Rutgers Biomedical Health Sciences), and Ze’ev Seltzer, DMD (University of Toronto)
Findings and Future Plans – Non-Technical Summary
The main goal of our study is to find genes that cause “Classical” Trigeminal Neuralgia Type 1 (TN1). This information will help clinician-scientists find cures that relieve patients’ severe chronic pain or prevent it from developing. Thus far, we’ve searched the genetic material (DNA) of TN1 patients at over a million places where people are known to differ from one another in their DNA letters (A, T, G or C). On average, any two people have about five million DNA differences between them. Most differences have no effect on health, but some cause or predispose to disease. Our challenge is to find the “needles in a haystack” that cause TN1, hidden among the millions of differences with no relation to TN1. We do this by comparing DNA of TN1 patients (cases) with that of people who do not have TN1 (controls).
Our initial search focused on 348 Caucasian TN1 patients, a modest sample size for human genetic studies today. Nevertheless, we are delighted to report discovery of several regions in the human genome with promising evidence they may harbor genes causing TN1. Some regions include only one gene, but there are 17 genes in the genome location with the strongest statistical support, including 3 with biological functions involving nerve degeneration, excitability of neurons or responses to nerve injury. These genes are strong suspects, but to determine which genes actually cause TN1we need a combination of: a) more genetic data of the kind we have already been gathering, and b) information from a complementary approach that uses high speed DNA sequencing. This further research is absolutely necessary before our initial discoveries are ready for testing in animals or translation to the clinic.
First, we must be absolutely certain our TN1 patients and controls do not happen to be very different by chance alone, but that the DNA differences occur because mutations hidden in the regions actually cause TN1. To do this, we will repeat our experiment a second time and see if we get the same results. We will analyze variation across the human genome for a new set of TN1 patients and controls using the most advanced genomic assays now available, more than doubling our sample size. If the same genome regions are again different in TN1 patients compared to controls (like lightning striking in the same place twice), this replication will confirm that TN1 disease-causing genes are indeed located there. Some regions have initial statistical support stronger than others, so these are more likely to be confirmed, but only by doing the assays and carefully evaluating what the data tell us will we know for sure which regions are confirmed. We do not expect all of our initially positive regions to be confirmed, but even if only one region is strongly confirmed this will be an extremely important advance, not only for TN1 but for the entire biomedical field of neuropathic pain in general. 2 Submitted January 3, 2018
Moreover, it is not enough to just find regions of the genome that harbor genes that cause TN1 – we also have to identify the specific genes and mutations in these genes that cause them to biologically malfunction, as this information is essential for translation to new therapies. It is possible that some of the mutations that cause TN1 are extremely rare, found only in TN1 patients and their close relatives. To discover additional TN1 genes and TN1-causing mutations, including those that are very rare, we will use the latest technologies for “reading” the DNA sequence of the entire human genome in a select subset of our TN1 patients. This method is called Next Generation Sequencing (NGS), and we propose to perform this assay for 100 TN1 patients.
Combining our previously-studied as well as our new TN1 cases gives us a sample of approximately 900 TN1 cases, of mostly Caucasian racial origin but with some non-Caucasians included too. Combining these with a similar number of controls will provide us with substantially increased statistical power to ask several very important questions such as the following: Do different genes cause TN1in young patients versus those who experience their first symptoms when older? (We already started to ask this first question in a limited way in the first phase of our research and with a larger sample can address this more rigorously.) Are there different genetic effects in males versus females, as found in many other genetic diseases? Are there different genes causing TN1 in the (typically younger) patients without vascular compression of their trigeminal nerve compared to patients whose trigeminal nerve has been damaged by years of vascular compression?
Our research may lead to a more complex picture of TN1 as being caused by not just mutations of just one gene, but in fact mutations found in several different genes may be associated with various subtypes of TN1. Genetics may reveal TN1 clinical subtypes that we currently do not even recognize exist, as has been found in numerous other neurological conditions including the epilepsies and the many forms of ataxia caused by different genes. While our primary goal remains identifying gene mutations that cause TN1, the research described here for the next phase of our study may also identify genetically distinct subgroups of TN1 patients as a very important secondary benefit of our genetic approach. Progress towards a cure (or, more likely, “cures”) will be more rapid and have greater chance of success if it is built on a foundation of knowledge about what is really going on biologically in different TN1 patients rather than if forced into a “one size fits all” therapeutic approach.
Project Timeframe: With adequate funding all research can be completed within one year. 3 Submitted January 3, 2018
Genetics Study
Brings Precision Medicine
To Trigeminal Neuralgia
By Scott Diehl
The Genetics Study team supported by the Foundation has completed a search of over one million locations in the DNA of 348 Trigeminal Neuralgia (TN) patients. This “Big Data” effort has pointed to genes affecting excitability of neurons, nerve degeneration and responses to nerve injury. These genes are very strong suspects, and the team will now gather additional information from more patients and from a complementary approach that uses high speed DNA sequencing.
In the team's next effort, these genes will be tested in a new set of TN patients.
If the same results are found again, this replication will be like lightning striking in the same place twice and confirm that mutations in these genes cause TN in some patients. These next steps are essential to confirm the initial findings and they may also reveal additional genes not detected with a strong enough signal in the initial search. Once confirmed, these discoveries will then be ready for testing in animals and translation to patients in the clinic.
The genetics data gathered thus far are painting a complex picture of TN as being caused by not just mutations in any one gene. It appears more likely that several different genes are involved in different patients, a phenomenon known as “genetic heterogeneity.” For example, one of the most strongly supported genes is important only for TN patients whose symptoms first appeared after age 55. A different gene with different biological functions is implicated in patients who developed TN at a younger age. Genetic heterogeneity has been found in other neurological conditions including the epilepsies and the many forms of ataxia caused by different genes. This strategy, known as Precision Medicine, is a major US and International effort getting underway focusing on nearly all human health problems today (https://allofus.nih.gov/).
While the primary goal of the genetics study is to identify gene mutations that cause TN, this research may also identify genetically distinct subgroups of TN patients as a very important secondary benefit. Progress towards a cure (or, more likely, “cures”) will be more rapid and have greater chance of success if built on a foundation of knowledge about what is really going on biologically in different TN patients rather than if forced into a “one size fits all” therapeutic approach.
The Genetics Study Team supported by the Foundation is an international collaboration of leaders in the fields of neurosurgery, pain biology and human genetics at Oregon Health and Science University (Dr Kim Burchiel), The Hebrew University of Jerusalem (Dr Marshall Devor), the University of Toronto (Dr Ze’ev Seltzer) and Rutgers School of Dental Medicine (Dr Scott Diehl). Numerous additional locations have provided valuable assistance with recruiting patients.
First Published Sept 23, 2014
We’ve come a long way! Join us and make our journey shorter!
By Roger Levy
Back in 1990, when the Trigeminal Neuralgia Association was first organized, its growth and development depended on the volunteer founders and some leading neurosurgeons who were concerned that little was being done to help patients understand their condition and gain access to specialists who could treat their condition. The Internet had yet to develop and getting the word out was managed through support groups started by volunteer patients who had become acquainted with the Association.
As time went on and the number of patients who looked to the Association for information and support began to grow so did the association’s awareness of the limitations which affected the medical and surgical options available as treatment. The drugs, after all, do nothing but dull the pain and most of the surgical procedures involve permanent damage to the nerve and that damage can often result in increased and, sadly, inoperable pain if the procedure fails. Gamma Knife treatment which involves radiation is promoted by many centers as non-invasive and yet there are too many patients who have increased pain where the radiation treatment failed. Even microvascular decompression which has a high success rate and involves no permanent damage to the nerve has its limitations because it involves a hospital stay and general anesthetic, for which some patients are not candidates either through choice or some other medical condition.
Still, over the years, the Association has helped many tens of thousands of patients to gain relief and regain a good quality of life. This is an important and continuing part of the Association’s mission on which it continues to deliver. But what of tomorrow’s patients or those today with unresolved pain? What’s to be done about them?
That is a question which the Association began to address when your Founding Trustees, Michael Pasternak, Mike Hirsch and I were members of the Association’s Board. Faced with that challenge, we embarked on an ambitious plan to establish a facial pain research program at the McKnight Brain Institute at the University of Florida, where Doug Anderson, Foundation trustee, was then the Executive Director. However, raising sufficient funds for research and meeting other parts of the Association’s mission was too great a challenge. Thus we chose to establish The Facial Pain Research Foundation.
That was over two years ago and look how far we have come! In a short period of time, The Facial Pain Research Foundation has raised over $1,300,000 and has provided funding for 4 separate research projects intended to find a permanent end to the pain of trigeminal neuralgia. Now, as word gets out across the internet via our Web Newspaper, people are contacting us from all over the world to ask “How can we help?” - Something unimaginable in 1990. When I was diagnosed with TN in that year, there were few places to turn. My neurologist could only recommend Tegretol or, when I proved allergic, acupuncture. Surgery, he warned me, was to be avoided at all costs. It was not until 1997 that the internet lead me to the Association and to a quick path to relief through microvascular decompression. Even with all those years of pain, though, I count myself lucky now that I am pain and medication free. Not every patient enjoys that success and for them and the patients who have yet to come, the work of the Foundation is imperative.
If you are reading this, chances are you are doing so because of the reach of the internet and, so rather like the support groups of the ‘90s, you have the opportunity to support our cause and bring our journey to a successful conclusion more swiftly. You can help in many ways as you can read elsewhere in our Newspaper, including making a financial contribution. Contributions are now coming to us almost daily with words of support and encouragement. No amount is too small to win our gratitude or to help.
We have world class scientific investigators enthusiastically working on behalf of facial pain patients, without national or other boundaries. They are our researchers “sans frontieres” and the benefits of their research will similarly lack borders. We are a community brought together by common cause. Be part of that community and help us to achieve our goals.
The Long Pain Road
For Chris Nolze
By
Kathleen Sweeney
Chris Nolze was diagnosed with brain cancer in 2007 at the young age of twelve. It was his initial diagnosis and the first of his major medical health issues.
He received radiation treatment after they did a biopsy on the tumor and placed a shunt in his head. It seems that where the tumor was located there was a lot of spinal fluid built up in his skull that was not draining. It was only the beginning of a number of challenges to follow.
During and after the radiation treatment he wasn’t “presenting” as well as other patients. They were not sure what was going on. There were signs of other medical issues that kept coming up and they are finally now discovering that the medical issues he has been dealing with since that time “are related either directly or correlated, to the radiation treatment”.
“Ever since my cancer I’ve had over 20 surgeries; … the majority of them were considered to be brain surgeries. Between the trauma from the tumor and then the trauma from all of the surgeries and then the trauma of radiation treatment my nerves were put at high risk … My cranial nerve and my trigeminal nerve just happened to be in that mix. “
When Chris had his wisdom teeth removed in 2012 he had complications that resulted in dry sockets. He was in pain but both he and his doctor thought it was due to the surgery. But it didn’t go away. Finally his dental surgeon suggested that they look into trigeminal neuralgia. It was a stretch since he did not fit the “norm” being a young boy with pain on both sides that was constant.
Neither Chris nor his parents had ever heard of trigeminal neuralgia. But since they had tried every possible medication at least twice and then in combinations and none of them gave him any relief they sought out his neurologist.
His neurologist and oncologist both thought it was highly “unlikely” that he had TN since he wasn’t showing the “proper” symptoms. Besides, it “just wasn’t possible”! For the next six months his parents took him all over this country looking for a doctor who would have another diagnosis.
Eventually they found Dr. Ben Carson in Maryland who tested the nerve on the right side of his face with a Rhizotomy treatment, which is the numbing or affecting of the nerve directly to see if it is the cause. “It helped the pain completely! … It was definitely a breath of fresh air.” It was the first relief he had had in six long months. “But I still did have constant pain on my left side.“
Shortly thereafter Dr. Carson scheduled Chris for an MVD (micro vascular decompression) on the other side, the left side. As he was recovering from that surgery the Rhizotomy “gave out” on the right side so they scheduled him for another MVD on the right side this time.
The pain was relieved but the incision would not close. They discovered that the skull bone itself was infected. They brought in a plastic surgeon to remove a piece of the skull about the size of a quarter. He placed a mesh plate over the opening created and then pulled the muscle up and over it (some of which had also been removed.) Eventually the incision closed properly.
Chris was pain free for about a year.
Then both sides came back and at about the same time. And around this same time he also contracted a rare case of intractable singultus (out of control hiccups). His is only the third case in medical history with this particular form. “They were speeding up on a daily basis and it got to the point where I would be doing over 200 hiccups in a minute! And it just kept getting faster and faster.”
It was a chiropractor, thinking outside the box, who put pads near his mesh plate and connected a tens unit to it. When it was turned on the hiccups stopped “instantaneously!”
So began another search for another doctor, this time with a tens unit connected to his head! Chris and his parents traveled the entire country again, finally finding Dr. Mark Linskey in California. He was actually Chris’ last and final hope of not having to live the rest of his life with a tens unit taped to his head.
“In every sense of the word, Dr. Linskey saved my life” says Chris. An MRI showed compressions on both his brain stem and on his facial nerves. Dr. Linskey thought the compressions on Chris’ brain stem might be the cause of the hiccups. While performing a repeat MVD on the right side of his face he tried lifting two major arteries off the brain stem. The hiccups stopped.
Out of curiosity and for research sake, Dr. Linskey released them and allowed them to go back where they were and the hiccups started back up again. When he lifted the arteries, they stopped. This confirmed that the cause of the hiccups was finally found! Since that surgery his right side has been not only TN pain free but he hasn’t had an abnormal case of hiccups since.
Once Chris recovered from that surgery they did a repeat MVD for trigeminal neuralgia on the left side. That was in 2014 and he is still pain free to this day!!
Although he cannot do any activities that might cause trauma to his head and has to avoid all sports, Chris is able to work part time. He is also studying online for his college degree, which he plans to receive this year.
In that same year of 2014, he joined the Young Patients Committee of the Facial Pain Association. It is a small group of less than 10 people who are supportive of anyone with facial pain under the age of 40. They promote awareness and help research for the really young suffering from all types of facial pain (not just trigeminal neuralgia.)
Chris also started his own foundation after his bout with cancer. He wants to give back to the community who “gave to my family and myself as we were going through everything. … I also wanted to raise funds for medical research for a lot of these radical conditions out there, especially trigeminal neuralgia.
“I focus on raising funds for research … and I have actually raised and donated $692 from my foundation to the Facial Pain Research Foundation” by selling teal colored t-shirts with his foundation logo on the front. A school friend of his hand knits teal scarves and he sells them also. All proceeds are donated to FPRF.
Chris does all he can to get the word out and to bring awareness. He has been recognized by the mayor of his town in Tom’s River, New Jersey, a couple of times already, with township proclamations that show that his foundation’s efforts are being recognized. He received one in 2016 from Governor Christy proclaiming October 7th Trigeminal Neuralgia Awareness Day! Since then, Chris has also received multiple proclamations from the town council recognizing every time the foundation helps out or works to spread awareness.
Chris volunteered that he wouldn’t change a thing if he could. “It helped sculpt me into the man I always wanted to be, that I was meant to be, and even if I had the opportunity to somehow stop everything from happening and go back in time and just live it out as ‘normal’ I wouldn’t change anything.” He is very insightful for his age. And very brave I might add.
When asked for what advice he would give to anyone new to the pain of trigeminal neuralgia he replied “The number one piece of advice I would give is to not give up and to not lose hope because even though you may be faced with a hundred people saying ‘No. It’s not possible.’ that doesn’t mean that there is absolutely no help out there for you.” And “Let your heart kick in and just say ‘no I’m not going to give in until I get the answers - until I get the proper treatment. I know something wrong is going on right now.’”
He added “It made me grow up much faster than I anticipated but in a way it also helped me.” I can vouch for that. Chris certainly seems a whole lot older and wiser than any 22 year-old I’ve ever known!
First Published June 13, 2014
Dr. Mark Linskey is a Professor of Neurological Surgery currently practicing at the University of CA, Irvine, in Orange County, CA (http://www.faculty.uci.edu//profile.cfm?faculty_id=5322). He trained in microvascular decompression (MVD) for 7 years with Peter Jannetta and in Gamma Knife stereotactic radiosurgery (GKSR), glycerol rhizotomy and radiofrequency lesioning for 7 years with L Dade Lunsford at the first US gamma Knife unit at the University of Pittsburgh. He has continuously served on the Medical Advisory Board of TNA - The Facial pain association since 2003; currently serving as their Western Regional Director. In practice and out of training for more than 20 years, he published the first prospective cohort comparative clinical trial of MVD versus GKSR for typical trigeminal neuralgia and is an internationally-recognized expert, and experienced surgical subspecialist, in trigeminal neuralgia. He is currently the American College of Physicians (ACP) Trigeminal Neuralgia module editor for their physician point of care decision support tool "Smart Medicine" (formerly PIER - Physician Information & Education Resource). He is also the Co-Editor of the Trigeminal Neuralgia module for the rigorous evidence-based medicine periodic systematic review tool and physician decision-support resource, "Clinical Evidence", published by the BMJ (British Medical Journal) for the British Medical Association.
Facial Pain The Research Imperative
By Mark E. Linskey, M.D.
From a twisted and perverse perspective, among facial pain patients, patients with classical trigeminal neuralgia (TN), are comparatively fortunate. We at least have surgical treatment options with reasonable chances for successful pain relief when current medical therapy fails. Yet even for TN patients, not all patients fare well. While in expert and experienced surgical hands, microvascular decompression (MVD) can lead to durable complete pain relief in about 80% of patients, this still leaves one in five TN patients still suffering. Patients seeking care in the general medical community are not so fortunate. MVD results can vary significantly surgeon-to-surgeon. Empiric experience over the last 20 years in my practice, would suggest that the success rate among less experienced and expert surgeons might run as low as 50%.
For those patients with multiple sclerosis-related TN, or who fail MVD, their plight can be improved with palliative destructive procedures directed towards the trigeminal nerve [stereotactic radiosurgery (SR, radiofrequency lesioning (RFL), glycerol rhizotomy (GR), and balloon compression (BC)]. However, these procedures serve best as temporizing measures, with up to 50% of patients with classical TN recurring within five years of the procedure. Each palliative destructive procedure runs the risk of facial numbness with its associated risk of new de-afferentation pain from nerve damage, and these risks accumulate and compound as destructive procedures are repeated. Thus overall, across the U.S., even for patients with classical TN, surgical intervention may realistically not provide adequate or long-lasting relief in an estimated 30-50% of cases.
But what about those patients with other forms of facial pain? In 2008, after 18 years of existence, The Trigeminal Neuralgia Association (TNA) changed its name to TNA – The Facial Pain Association (TNA-FPA) in recognition of the fact that patients with facial pain other than classical TN also needed education, support and help too. These conditions include TN2, neuropathic facial pain, facial pain of obscure etiology, and anesthesia dolorosa, among many others. For these patients, MVD rarely leaves a patient pain-free. Furthermore, while palliative destructive procedures can, and do help, they not only are less successful than for classical TN patients, they may actually worsen the situation through increased de-afferentation, despite the best of surgical intentions. While surgical stimulator surgery can help these patients in very select cases, the overall percentage of patients enjoying significant and durable relief is disappointingly small. If we now broaden our inquiry to include all facial pain patients that seek help from TNA-FPA, it seems likely that only about half will achieve adequate or long-lasting relief from their suffering through surgery. Clearly surgery alone is not the answer for too many of our patients, friends, and family who suffer from facial pain.
The word imperative refers to something that is both necessary and of vital or crucial importance. It may also refer to the expression of a command. For facial pain syndromes new discovery and therapeutic breakthroughs through basic science research is an absolute imperative in the first sense and an imperative from our patients and their loved ones in the second sense.
We know that vascular compression is a necessary cause for the majority of classical TN patients. Yet up to 40% of normal living patients and up to 50% of patients studied at autopsy have these vascular contacts without having TN. Clearly vascular compression, while necessary, is not sufficient. The logical additional factor, that many have speculated about, likely involves additional predispositions related to genetics and/or the biology of myelin nerve insulation, axonal damage, or both. In my opinion, studies of deferential gene expression comparing classical TN patients to normal population controls carry the highest chance of uncovering potentially new fruitful areas for investigation and future therapeutic exploitation for patients with classical TN.
While the hoped for discoveries from studying differential gene expression in cases of classical TN might be more generalizable to help patients with other facial pain syndromes, this is by no means certain. Thus, simultaneous additional lines of research inquiry are also desperately needed. These include the urgent need for a better understanding of the neurochemistry and the psycho-biology of chronic neuropathic pain and the fast-track development of new agents for clinical testing. It includes studies into the biology of nerve repair and regeneration, through both pharmacological means as well as potential cellular therapies including stem cells. It also includes the need to study safe means of modulating pain perception at the brain level through brain stimulation technology.
While it is simple and conceptually satisfying to talk about the search for one “cure”, this may be an elusive goal given the heterogeneity and wide variety of facial pain syndromes suffered by patients seeking help through the TNA-FPA. More than one “cure” may be needed depending on the individual circumstances of each patient. Yet the quest for a “cure”, whether one or many, all still depend on basic science research advances which are expensive and which take years to develop, test and realize.
As a surgeon, I long for the day when we have therapies that can increase our MVD results to near 100% success, as well as offer hope and more predictable treatment success chances to our non-classical TN facial pain patients. While I am biased by my surgical background, I doubt that these advances will involve a new pill distributing an agent non-specifically throughout our body. I strongly suspect that they will involve therapies that will be most effective locally and selectively at the site of pathology or damage, either through direct open surgical application, or needle or electrode delivery into the trigeminal nerve root, ganglia, or brain. Thus surgery will likely be an important component of any success realized through our research efforts.
If we wish the state of care for patients with facial pain to improve from the levels currently available, we are indeed faced with a research imperative. The need is great and the costs are considerable. The best way that most can help is through generous donation and ongoing, sustained, support for efforts such as those fostered by our own Facial Pain Research Foundation http://www.facingfacialpain.org/ . We need everyone’s help and support to drive this mission forward and ultimately succeed.
