2022 Symposium Overview- Winter 2022 Newsletter

2022 SYMPOSIUM OVERVIEW

OROMANDIBULAR DYSTONIA AND MEIGE SYNDROME

PRESENTED BY VIRGILIO GERALD H. EVIDENTE, MD

REPORTED BY HEIDI COGGESHALL

Dr. Virgilio Gerald Evidente of the Movement Disorders Center of Arizona presented an overview of Oromandibular Dystonia (“OMD”) and Meige Syndrome. His presentation contained many videos of the dystonia, including patients who have had success with treatment. The BEBRF strongly encourages any patient with OMD to view the presentation online in our website to see these videos. OMD refers to the forceful muscle contractions of the mouth area, jaw and/or tongue. Other terms for the disorder include: orofaciomandibular dystonia, orofacial buccal dystonia, lingual dystonia, jaw dystonia, cranial dystonia and facial dystonia. OMD interferes with the opening/closing of the jaw and it affects chewing and speech. Jaw opening is more common than jaw closing. Speech is mainly impaired with jaw closing dystonia, which Dr. Evidente demonstrated by talking with his jaw clenched shut. Because of the clenching, some patients first go to speech pathologists or TMJ specialists whereas the main pathology is dystonia. Typically, about 50% (or a little bit more depending on the study) of blepharospasm patients develop OMD. When the blepharospasm spreads to the jaw, the disorder is referred to as Meige syndrome, named after the French neurologist Henri Meige. Meige does not usually start with jaw dystonia first and then spread upwards to blepharospasm. If it does, it typically starts with patients with tardive dyskinesias or tardive dystonias.

Brueghel’s syndrome was coined by Dr. David Marsden in 1976 (alluding to the De Gaper painting in 1558, pictured below) which is blepharospasm and OMD. Interestingly, the famous painting is only someone yawning but it still depicts Brueghel’s syndrome well. For some patients (but less common), the dystonia spreads to the neck in craniocervical dystonia but this is typically in tardive rather than idiopathic patients. The risk factors for Meige spread tend to be: previous head or face trauma with loss of consciousness, females and/or older age at onset. Spontaneous remission of Meige is less than 10%. In his clinical practice, remission is rare.

OMD/Meige typically begins later in life with an average age at onset of the mid-50s, affects more women than men and affects about 69 per 1 million Americans. Triggers are speaking, chewing, eating and stress. Usually, labs and brain MRIs are normal. Sensory tricks may give positive relief but typically with jaw opening

ViRGILIO GERALD H. EVIDENTE, MD

The Benign Essential Blepharospasm Research Foundation (BEBRF) is a nonprofit, 501 (c) (3) organization founded in 1981 by Mattie Lou Koster, a blepharospasm patient.

Blepharospasm (BEB) means eyelid spasm. The eyelids unpredictably and involuntarily clamp shut in both eyes, leaving the victim functionally blind until the spasm ceases in a few seconds or a few minutes.

Cranial dystonia (Meige) is a similar condition in which involuntary muscle spasms in the lower face and jaw cause grimacing and jaw movements.

Blepharospasm and cranial dystonia (Meige) are classified as movement disorders and are described as focal dystonias.

Hemifacial spasm generally begins as an involuntary contraction around one eye that gradually progresses down one side of the face to the cheek, mouth, and neck. It is not a form of dystonia.

BEBRF is a member of the National Organization For Rare Disorders (NORD), American Brain Coalition,Dystonia Advocacy Network, Dystonia CoalitionORDR, and The Harvard Brain Tissue Resource Center (Laurie Ozelius, PhD is the BEBRF Representative).

Benign Essential Blepharospasm Research Foundation

755 S. 11th St, Ste 211

Beaumont TX, 77701

P.O. Box 12468

Beaumont, Texas 77726-2468

Phone: 409-832-0788

Fax: 409-832-0890

E-mail: bebrf@blepharospasm.org

Web site: www.blepharospasm.org

Contributions may be sent to: BEBRF

P.O. Box 12468

Beaumont, Texas 77726-2468

The Editorial Staff reserves the right to edit any and all articles. It is our editorial policy to report on developments regarding blepharospasm, cranial dystonia and hemifacial spasm, but we do not endorse any of the drugs or treatments in the Newsletter. We urge you to consult with your own physician about the procedures mentioned.

The Blepharospasm Newsletter is published quarterly and mailed to patients, families, doctors, friends of the Foundation, and health care providers around the world.

Newsletter suggested donation $20.00 USD

DEADLINE DATES

EXECUTIVE DIRECTOR

New Webinar: BEBRF will be presenting a new Webinar via Zoom, Managing Dry Eye, with presenter Rebecca Petris, Executive Director and President of The Dry Eye Foundation, on Friday, February 24, 2023 at 1:00 central time. In order to attend, you must register and then Zoom will email you a link to get into the Webinar. There are registration links on the BEBRF Facebook page, on the BEBRF Website under the ‘Events’ link then under the ‘Webinars’ link. Or you can email me at charlene@blepharospasm.org. Rebecca has spoken across the globe on many topics related to dry eye. We will continue to have ongoing Zoom Support Group Meetings. In addition, we will have a special meeting for residents of the Eastern District on Thursday, February 16th and for the residents of the Central District on Wednesday March 29th. More details are on page 14. We will be setting up a Western District meeting for April or May.

PROTECTING PATIENT INFORMATION:

The Benign Essential Blepharospasm Research Foundation respects the privacy of patients. Patient information is not shared outside the BEBRF organization.

TABLE OF CONTENTS

The opinions expressed in the articles in this newsletter are those of the authors and do not necessarily reflect the views of the BEBRF, publisher of the BEBRF newsletter.

For your information, Support Group Meetings are never recorded so that participants can feel free to share. Also, every Zoom Support Group Meeting has a different link, so if you want to attend one, you must contact me in advance to receive the appropriate link. In addition to listing the upcoming Support Group Meetings in this Newsletter, they are also listed on both the BEBRF Website and Facebook page.

BEBRF attends various medical academies to raise awareness of blepharospasm and its related disorders and to inform healthcare practitioners of all the services that BEBRF offers for patients (see related story on page 11). In 2023, BEBRF hopes to attend the North American Neuro-Ophthalmology Society’s Academy in Orlando, FL in March, the American Association of Optometry Academy in New Orleans, LA in October, and the combined American Society of Ophthalmic Plastic and Reconstructive Surgery and American Academy of Ophthalmology in San Francisco, CA in November. All videos from the 2022 BEBRF Symposium in Phoenix are now available on our website. If you would like to watch them in ‘full-screen’ format, simply click the white square in the lower right hand corner of the small, inset video screen. You can find the videos under the ‘About Blepharospasm’ link and then under the ‘Videos’ link.

At the December, 2022 National Zoom Support Group Meeting, Dr. Laurie Ozelius (who is on the BEBRF Medical Advisory Board) and Dr. Nutan Sharma, both of Harvard Medical School, made a joint presentation on a new research project for which they had just gotten funding from the National Institutes for Health. This will be a five-year project on facial dystonia, including blepharospasm. As soon as they have their project set up to begin, they will need blepharospasm and other facial dystonia patients to participate. Some will be able to participate in person, but many will be able to participate remotely. When BEBRF receives all of the participation information, we will post it on our Website and Facebook page as well as reporting it in the Newsletter.

BEBRF BOARD OF DIRECTORS

Heidi Coggeshall, President/Treasurer*

Tishana Cundiff, Vice PresidentEducation & Support*

Peter Bakalor, Vice PresidentDevelopment*

Jane Boyd, MD, Vice PresidentPhysician Outreach*

Charlene Hudgins, Executive Director/Secretary

Cynthia Clark*

Robert Campbell, PhD*

Jonathan Healy

Carlas Powell*

Bryan Renehan*

EX OFFICIO

Brian Berman, MD, Advisor

*Patients

MEDICAL ADVISORY BOARD

Brian Berman, MD, Chair, Richmond, VA

Mark Hallett, MD, Bethesda, MD

Andrew Harrison, MD, Minneapolis, MN

Joseph Jankovic, MD, Houston, TX

Hyder A. “Buz” Jinnah, MD, PhD, Atlanta, GA

Laurie Ozelius, PhD, Boston, MA

Sarah Pirio Richardson, MD, Albuquerque, NM

Charles Soparkar, MD, PhD, Houston, TX

Mark Stacy, MD, Greenville, NC

Julie Woodward, MD, Durham, NC

DISTRICT DIRECTORS & EMAIL

Bryan Renehan, Eastern CT, DE, DC, FL, GA, MA, MD, ME, NH, NJ, NY, NC, PA, PR, RI, SC, VT, VA, WV dir-e@blepharospasm.org

Tishana Cundiff, Central AL, AR, IL, IN, IA, KS, KY, LA, MI, MN, MS, MO, ND, OH, SD, TN, TX, WI dir-c@blepharospasm.org

Cynthia Clark, Western AK, AZ, CA, CO, HI, ID, MT, NE, NV, NM, OK, OR, UT, WA, WY dir-w@blepharospasm.org

rather than jaw closing dystonia. Tricks include touching the lip or chin, chewing gum or biting on a toothpick. Dr. Evidente showed some video examples of patients with improvements by sensory tricks. In one case, the patient’s speech was drastically improved by just holding some plastic in his mouth. The patient also held their jaw which helped. Dr. Evidente has seen more gum chewing in his practice as a sensory trick.

There is no known cause for primary or idiopathic dystonia. About 10% of patients of meige/bleph have a family history of some type of dystonia.

Other symptoms include: nasal contractions, facial grimacing, lip pursing, sucking, bruxism, tongue dyskinesia, mouth corner retraction and platysma spasms. The dystonia can cause a slurring of speech or breathing difficulty. Some have asked what is the difference between bruxism and OMD-induced jaw clenching. Bruxism (which is quite common) only occurs while sleeping versus OMD-induced jaw clenching stops while sleeping. Patients with bad dystonia get relief when they go to the sleep as most movements disappear during sleep.

Given that OMD affects the jaw muscles, patients can have muscle pain, headaches, facial pain and TMJ pain. For jaw closing dystonia, many patients seek TMJ specialists because the TMJ joints are worn down, which accelerates the arthritic process. There is no known cause for primary or idiopathic dystonia. About 10% of patients of meige/bleph have a family history of some type of dystonia. Secondary causes include drugs, neuroleptic exposure, stroke, etc.

Jaw dystonia appears in a few ways: jaw opens, jaw closes, jaw protrudes forward or jaw deviates laterally.

Tongue dystonia appears in a few ways: tongue protrusion, tongue retraction or tongue deviates towards one side.

Which JAW MUSCLES should be injected?

Oral medications may be used. He reviewed the categories and side effects. Anticholinergic drugs are best tolerated by younger patients. Examples are: Benztropine (Cogentin) and Trihexyphenidyl (Artane) and side effects include dry mouth, dry eyes, blurring of vision and others. Benzodiazepines include clonazepam, diazepam. Side effects include sedation, confusion, imbalance and dizziness. Over the last few years because they are so addictive, it is increasingly harder for doctors to prescribe these medications. For example, only one month can be prescribed at a time. It can be difficult to wean off these drugs. Muscle relaxants include baclofen, tizanidine and cyclobenzaprine. Side effects include sedation, confusion, imbalance and dizziness. Antiseizure drugs include gabapentin and topiramate. They are most effective for earlier blepharospasm but less for OMD. Parkinson’s medicines of levodopa, dopamine agonists and anticholinergic drugs may be used but best for Parkinson’s disease – related OMD. They are effective in Dopa-responsive dystonia. Neuroleptics such as haloperidol, perphenazine and risperidone can be effective for OMD but they paradoxically can cause different movement disorders of tardive dyskinesias. Some of these movements can be permanent. These drugs are used more widely now and tend to be used for depression, bipolar disorder and nausea. For Tardive Meige, some dopamine depleters/ VMAT2 inhibitors are the best drug treatment.

Dr. Evidente next showed a video of a patient with “Lubag” which is hard to treat because of the severity of the dystonia. There is a limit of how much botulinum toxin a patient can receive. In one case where the treatments were not working, the tired patient asked for a sleeping pill because of the relief he received

during sleep. The zolpidem (ambien) prescribed helped this patient. It didn’t help with sleep but did help with the dystonia. He also showed a video of a craniocervical patient with sounds of a type of gasping. He had good luck with tetrabenazine with this patient as shown in the video.

For OMD, Dr. Evidente may try the drugs first because botulinum toxin is less effective with OMD. The muscles for the injections are in the chart attached. If the wrong sites are injected, it can make the treatment ineffective or possibly make the dystonia worse. He showed a variety of videos of different jaw and tongue dystonias and the muscles being injected. The Electromyography (EMG) tool helps with some patients to find the correct placement for the toxin. If a patient needs injections into the tongue but it is inserted from the inside of the mouth, the risk is high because the bacteria in the mouth that can cause an infection. Tongue dystonia injections are more dangerous because excessive weakness of genioglossus can

cause obstruction of the pharynx and respiratory distress where the tongue goes back into the throat. For tongue injections, he uses the EMG and the tiniest dose possible.

Some patients have found physiotherapy helpful with exercises for the lips, jaw, tongue, cheeks, palate and facial muscles. The exercises can help reduce spasms, prevent contractures and lengthen muscle fibers. It promotes re-wiring of the brain (plasticity). Dental devices/oral appliances can also be helpful (typically via an orthodontist).

For Meige, some patients have a blepharoplasty (eyelid lift) that helped. Less toxin was required afterwards. Other surgeries are myectomy and selective neurectomy. Finally, he had some patients who did not have much success with toxin or medication but remarkable success with DBS (Deep Brain Stimulation). (But also, some patients that have not). There have not been many patients with solely blepharospasm using DBS.

DEEP BRAIN STIMULATION FOR BLEPHAROSPASM: WHAT DO WE KNOW?

PRESENTED BY FRANCISCO PONCE, MD |

Since the late 1980s, over 200,000 people have been treated with Deep Brain Stimulation (DBS), also known as neuromodulation, worldwide. This procedure is not new or futuristic. DBS has been around since 1986 and was approved by the FDA in 1997. The track record is that it is a safe, non-destructible, reversible, and adjustable therapy.

The first pacemaker for the heart was introduced in 1958. The deep brain stimulator is essentially a pacemaker for the brain: the device is implanted in the chest, just as the heart pacemaker, but the wires go under the skin, ascending through holes behind the forehead, through which electrodes enter the brain and basically tap into the circuit that goes awry with conditions such as dystonias.

Like many therapies, Deep Brain Stimulation is a product of an accidental discovery in medicine. During the early days of diagnosing Parkinson’s disease, James Parkinson noticed that a person

REPORTED BY HILLIARD KELLY PRUITT

who suffered from a stroke that affected his entire hemisphere had stopped shaking on that side of the body. This is where the idea of the role for surgery to treat movement disorders originated. That approach was refined during the 1900s from major operations to a wire that would essentially “cook” the brain. DBS is considered more of an electrical therapy for conditions like Parkinson’s and other types of dystonia rather than surgical treatment.

All movement disorders, including Parkinson’s, arise in the brain. Originally, these conditions were treated through lesions by creating a small “stroke” to disrupt the circuits causing them. DBS therapies pre-dated high quality MRI imaging, before precise detail and understanding of the cellular activity of the brain, electrophysiology, and circuitry was available. Consequently, throughout the 1990s, MRIs were not used for DBS. Procedures prior to 2012 were safe and effective, although it took a long time to pinpoint the right spot for the electrode. This required the patient to be fully conscious to provide feedback as to avoid causing irreparable damage due to a stroke. Many surgeons would only treat one side at a time due to the time commitment and patient’s level of discomfort.

The first pacemaker for the heart was introduced in 1958. The deep brain stimulator is essentially a pacemaker for the brain

Thanks to new advancements such as direct targeting using MRI, the increasing ubiquity of portable CT Scanners for

Francisco Ponce, MD

. . .

image guidance, and the Entropy CT Scanner GPS system during surgery to allow on-screen viewing, beautiful imaging is available with exquisite detail of the brain’s anatomy. Coupled with decades of experience performing the operation, the procedure now just has to be implemented accurately. In just the last 8 years, DBS has graduated from being an intervention of last resort to a treatment that can be implemented closer to the onset of the condition.

These improvements have taken a lot of the guesswork out of the procedure. When MRI targeting is combined with a portable CT scanner used in the operating room, a high quality photo from the MRI can be combined with the CT scanner as soon as the electrode is placed in real time. This can be compared to the surrounding brain obtained beforehand to ensure accuracy. When MRI targeting is combined with a portable CT scanner used in the operating room, the most desirable result is achieved: the patient can now be asleep during the operation.

Treatment of dystonia by DBS, including blepharospasm and Meige, was approved in 2003 through a Humanitarian Device Exemption (HDE). HDE is allowed when a condition is rare enough that a multi-centered, randomized blind clinical trial cannot be launched in the same way they do for pharmaceuticals and medications. HDE allows doctors to perform DBS for dystonia, which suggests adequate data to provide a benefit for patients with the condition.

The FDA describes their approval for dystonia under the following labeling: “primary dystonia, including generalized and/or segmental dystonia, Hemidystonia, and cervical dystonia (torticollis) in patients seven years of age or above.” It is under this description that conditions such as blepharospasm and Meige are treatable with DBS. Medtronic is the only company that has a Deep Brain Stimulator that has been FDA approved in the treatment of dystonia. There are about 88 patients, average age of 57, that have been described in various publications as having blepharospasm,

Different conditions have different latencies to the therapy. A patient with an action tremor may see the disorder stop immediately upon the pacemaker activation.

and who have undergone DBS treatment. Most participants had more than one symptom, which fits into the category of segmental dystonia. Best results for DBS for dystonia have been achieved in children and adolescents with the DYT1 mutation. The key to best outcomes come down to good patient selection, safe and accurate lead placement, and good programming.

Class 1 evidence supports that DBS has an effect on dystonia. Insuring best outcomes with Deep Brain Stimulation requires being under the care of the right neurologist, who determines patient selection, while the movement disorder specialist is trained to tease out alternative diagnoses that might not be as amenable to these types of therapies to insure a patient’s qualification as a candidate for DBS according to their experience. While the neurosurgeon’s role in treating conditions with these “brain pacemakers” on the team and journey is discreet, their purpose is to make sure this therapy is implanted safely and accurately. The task of the neurosurgeon is to find how to deliver the proven electrical therapy with the minimum possible risk. This is a surgery for quality of life, so the stakes are very high. Different conditions have different latencies to the therapy. A patient with an action tremor may see the disorder stop immediately upon the pacemaker activation. With other conditions, it could be days or sometimes weeks before any results are achieved, and will see a buildup of benefits over the course of months. The goal is to restore function, and the only way to gauge an operation’s success is if a patient can say their life has improved after six months, and they would do it again if they had the opportunity.

After decades of learning and research, a solid product is now being delivered. A new era of DBS is being ushered in. By speaking the language of the brain, using information about where the electrode is, and recording the activity within the brain, DBS will ultimately result in an intelligent pacemaker that knows where to go to maintain control. Advances in technology continue to open the door to smarter and more efficient programming through advanced control and understanding of the patient’s symptoms. While DBS is an option for blepharospasm, recommendation by a movement disorder specialist remains critical.

OVERVIEW OF BLEPHAROSPASM: RISK FACTORS, DIAGNOSIS, AND TREATMENT

“I love the BEBRF organization. I feel it has raised me in my career,” stated Dr. Padma Mahant in her opening remarks for “Overview of Blepharospasm Risk Factors, Diagnosis, and Treatment.” In 2001 as a fellow at the Barrow Neurological Institute in Phoenix, one of her projects with Dr. Mark Stacy and Dr. Elizabeth C. Peckham was a study involving BEBRF participants. This extensive survey included gathering blood samples key to the genetic research we have today.

That research paper, Clinical Features of Patients with Blepharospasm: A Report of 240 Cases, and a recent paper in 2021: Clinical Features and Evolution of Blepharospasm: A Multicenter International Cohort and Systematic Literature Review provided the information for Dr. Mahant’s presentation at the October 2022 Symposium. She reiterated the importance of BEBRF members participating in studies like these because blepharospasm is quite rare and under-diagnosed.

As a neurologist and specialist in movement disorders, Dr. Mahant continued with a definition of blepharospasm and, in the world of neurology, where does it fit in the Movement Disorder flow chart? These disorders are separated into two distinct categories: hypokinetic (too little movement) and hyperkinetic (too much movement). Blepharospasm falls into hyperkinetic and is grouped with Generalized Dystonia, Writers’ Cramp and Cervical Dystonia. Dystonia defined is “. . . sustained or intermittent muscle contraction; abnormal repetitive movements.” Dr. Mahant further explained blepharospasm specifically as “focal cranial dystonia (in the head); involuntary, bilateral (both sides) synchronous and sustained contractions of the muscles around the eyes.”

DIAGNOSIS & RELATED CONDITIONS

First, diagnosis can be delayed. In the review of

41 blepharospasm papers (over 10,000 patients) findings showed 50% of patients received correct diagnosis within one year of symptom onset; however, the median time from onset to diagnosis was two years, and nearly 1/3 of patients’ diagnoses was greater than five years after symptom onset. Interestingly, 60% of patients saw at least five physicians before definitive diagnosis.

Second, Dr. Mahant discussed how the diagnosis is made using quadrants of the face, differentiating:

(A) MYOKYMIA: one quadrant of face, upper or lower lid;

(B) HEMIFACIAL SPASM: two quadrants and one side of face;

(C) BLEPHAROSPASM: two quadrants, upper half of face; and

(D) MIEGE SYNDROME: four quadrants, entire face and neck.

MYOKYMIA VS. BLEPHAROSPASM

Padma Mahant, MD

She further explained the descriptors for each type with differing treatments as compared to blepharospasm.

Myokymia is sometimes called the “Medical Student Condition” or eyelid twitching or tics, possible side effects of too much caffeine, late nights, too little sleep, etc., and treatment being reduction of stress. Blepharospasm is both upper quadrants.

Hemifacial involves one side vs one upper lid; musculature involved is different with these contractions, and treatment is very different and could involve a surgery called microvascular decompression involving the seventh cranial nerve. The causes as well are very different from blepharospasm.

BLEPHAROSPASM SYMPTOMS & RISK FACTORS

Again referring to the two extremely important research papers, Dr. Mahant listed the data on just who is affected: While 2000 new cases are diagnosed annually, blepharospasm remains in the rare condition category with only 50,000 cases in the U.S or five in 100,000 cases nationally. Worldwide shows 20-133 cases per million, varying with geographic area; i.e., in Italy and Japan blepharospasm is more likely than cervical dystonia; but in Europe and the U.S., cervical dystonia is greater than blepharospasm. Average age of patients is 56 or in the 5th to 7th decade with data showing a female preponderance of 2.3:1.

Symptoms fall into two areas:

(1.) MOTOR FEATURES in order of frequency would be exaggerated or increased blinking; involuntary eyelid closure; twitching of eyelids and a powerful or sustained closure of eyelid.

(2) NON-MOTOR FEATURES, which Dr. Mahant pointed out often pre-date motor symptoms, include light sensitivity or photophobia experienced in 82% of patients; dry eyes 78%; gritty sandy, burning sensation in eyes 70%.

Other clinical symptoms may include tremor (22% associated head and/or hand tremor); Apraxia of eyelid opening or inability to voluntarily open eyes (10%-50% reported intermittent inability to open eyes in absence of spasm or muscle weakness). Finally, depression and

social anxiety symptoms were reported in both studies of several hundred patients with 24% showing depression based on the Beck Depression Scale (BD I-II) and 40% showing social anxiety using the Social Anxiety Scale (LSAS).

RISK FACTORS

Dr. Mahant then discussed findings from these extensive studies that listed long and varied risk factors including these: Age with two-thirds of patients age 60 and above; prior eye disease, especially conjunctivitis; eye surgery; trauma with head trauma found as an antecedent; family history showed 30% have 1st and 2nd degree relatives with blepharospasm or other dystonia; stressful event such as death, divorce, or moving; psychotropic and antiemetic use which are medications that oppose dopamine; white collar profession implying excessive screen use; and history of difficult or premature birth. An interesting protective factor, coffee, was found in both the original 2001 study and the second paper in an Italian cohort.

The question of risk of spread beyond eyelids and upper face was covered with 61% experiencing this but most spread occurred in the first five years after onset and most common regions were lower face and neck. Factors associated with spread beyond eyelids included family history of dystonia, apraxia of eyelid opening, and depression and social anxiety.

TREATMENT

Common treatments include oral medications, medical or surgical, and non-medical.

Oral Medications provide partial or transient relief and are less effective than botulinum toxin injections. Dr. Mahant listed anticholinergic medications which include trihexyphenidyl and benztropine which block the chemical transmission from nerve to muscle; but cautioned of the “whole host of negative side effects” including dry mouth, sedation, cognitive slowing, urinary retention, and constipation. Plus, these are systemic effects NOT seen with Botox injections. Other medications are the GABA-A (benzodiazepines: Klonopin, Xanax, Ativan, Valium) and GABA-B muscle relaxants (Baclofen and gabapentin). These too have side effects of sedation, slowing, trouble with balance and the potential for dependency as GABA-A

Myokymia is sometimes called the “Medical Student Condition” or eyelid twitching or tics, possible side effects of too much caffeine, late nights, too little sleep, etc., and treatment being reduction of stress.

is a controlled substance. The final dopaminebased medications include Agonists which mimic or increase dopamine with side effects of nausea, sedation, and blood pressure changes, then Inhibitors which block or prevent release of dopamine. Again, side effects are many (cognitive impairment, weight gain, Parkinsonism, tardive dyskinesia – or TD which is excessive movement that can be generalized and may not go away after stopping medications). Dr. Mahant stated that most movement disorder specialists DO NOT prescribe these. She concluded, “You are trading one problem for a more severe one.”

Medical Treatments: Botulinum toxin injections, first approved by the FDA in 1989 for medical indications (as the result of a BEBRF-funded research grant), remain the first line treatment for BEB. In a retrospective study, Dr. Mahant explained, “sustained benefits at two years after diagnosis is seen in 92% of patients.” Most are repeated every three months. Surgical treatment for intractable cases would be modified and partial myectomy where patients may see 88% improvement. Side effects are postoperative swelling, incomplete eyelid closure, numbness, and about ½ will still require botulinum toxin injections 5 years after surgery usually at lower doses. Dr. Mahant also described deep brain stimulation (DBS) or a brain

Botulinum toxin injections, first approved by the FDA in 1989 for medical indications (as the result of a BEBRF-funded research grant), remain the first line treatment for BEB. In a retrospective study, Dr. Mahant explained, “sustained benefits at two years after diagnosis is seen in 92% of patients.

pacemaker as a surgical treatment but usually for dystonia with BEB as a symptom.

Non-medical treatments or strategies include artificial tears and lid scrubs which help with the dry, gritty symptoms; dimmer lights and task lamps to manage photophobia; FL-41 tinted lenses that block more bothersome light wavelengths with studies showing 20% average reduction in blink frequency; stress reduction, and a new area of emphasis would be in supplements such as CBD.

In conclusion, Dr. Mahant stated despite all these treatment options, “We still do not have a cure. What I love about BEBRF is they are such a support for patients in handling the disability and provide resources.”

BOTULINUM TOXIN: INJECTION TECHNIQUES AND TOXIN CHOICES

PRESENTED BY JOHAN SAMANTA, MD | REPORTED BY TISHANA CUNDIFF

Dr. Johan Samanta, MD came to us with his approximately 25 years of experience as an injecting Movement Disorder

Specialist to share on the topic, “Botulinum Toxin: Injection Techniques and Toxin Choices.”

In a brief review of the history of botulinum toxin, he explained that, “botulinum toxins have been around well, honestly, for millennia,... described as far back as the middle ages.” Experimentation with “therapeutic use of botulinum toxins really began with the Cold War” in attempts to develop defenses for a potential attack. Shortly after, during the ‘60s and ‘70s, scientists began research on isolating proteins and toxins to find

therapeutic benefits of using a small dose of a purified toxin. In 1978, Dr. Alan Scott, an ophthalmologist, began human trials of what he called “oculinum toxin” for treatment of patients with strabismus (“lazy eye”), hemifacial spasm, and blepharospasm*. Dr. Samanta then shared the slide below and outlined the medical advances that have brought us to the current FDA approved uses of botulinum toxins of Botox ® (Type A) in 1989 for blepharospasm, strabismus, and hemifacial spasm; Myobloc ® (Type B) in 2000 for cervical dystonia; Dysport ® (Type A) in 2009 for cervical dystonia; and Xeomin ® in 2010 for cervical dystonia and blepharospasm.

Dr. Samanta further explained the difference between the medical FDA approvals and “on-label” versus “offlabel” uses based upon the initial research. He gave the example of the decade-long “off-label” use of aspirin to effectively prevent heart attacks although that was not its original indication. Currently, while only two of the four toxins are officially indicated for Blepharospasm, this does

Johan Samanta, MD

BLEPHAROSPASM AND BOTULINUM TOXIN

► 1978 Dr. Alan Scott begins human trial of “oculinum toxin” for strabismus, hemifacial spasm, and blepharospasm

► 1989 FDA approves Botox for blepharospasm

► 2000 FDA approves Myoblock (type B) for cervicle dystonia

► 2009 FDA approves Dysport for cervical dystonia

► 2010 FDA approves Xeomin for cervical dystonia and blepharospasm

not suggest “that we can’t or we shouldn’t use the other toxins.” Most insurance coverage guidelines, “Medicare, for instance, really treats all four toxins as equivalent” in terms of treatment but not in terms of dose. Often, insurances are impacted due to the financial side of the medications.

Botulinum toxin is essentially the treatment of choice for blepharospasm, and based upon the data, it seems to lead to “a far higher response rate…by a second or third round of treating someone: 90% or 90+% of individuals are going to have seen a marked improvement of 70% or better in their blepharospasm symptoms.” In contrast, oral medications yield “maybe 25% or so response rates.”

Samanta explained, “The idea behind botulinum toxin is trying to dial down the signal coming into that muscle.” He reminded the audience that the goal is not to turn off the nerve signals completely but rather to attempt to bring them within a range of normal functioning. The effects are temporary.

scissors. It just clips whatever protein it has been designed to clip.” He used the analogy of a lawn mower just clipping grass with the reminder that the grass will grow back.

“Typically, the peak or the full blockade of a treatment is going to be reached at about 15 days,” rather than instantly. Then there is a period of a plateau. Over the next 12 weeks approximately, there is a gradual decline. Towards the end of that time, it is common to experience a gradual return of symptoms. Samanta said, “typically the duration of the benefit is somewhere between 12 and 14 weeks.” He continued to remind us that patients vary in the time they experience relief, likely due to metabolism rather than technique.

He further reminded us that although botulinum toxins are the treatment of choice, “every treatment has the potential for some adverse effects.” The most common ones noted are drooping eyelids (ptosis), dry eyes (likely under-reported), and double vision. Fortunately, these side effects are not permanent; both the injection sites and dosages can be adjusted with future injections. He reminded the audience that patient feedback is vital in aiding the physician in both increasing effectiveness and reducing adverse sideeffects.

In efforts to lower the chances of reduced effectiveness, he stressed the importance of not seeking booster treatments, or even cosmetic Botox treatments in the region between treatments as this can impact antibodies. If other injections are introduced, it is important to share that information with your physician.

In efforts to lower the chances of reduced effectiveness, he stressed the importance of not seeking booster treatments, or even cosmetic Botox treatments in the region between treatments as this can impact antibodies.

Of the four toxins, three of them are based on Type A botulinum toxin; Myobloc is based upon Type B. All of them have slightly different properties from a biochemical standpoint, creating differences in the way they are stored, reconstituted, the unit potency, and the recommended dosage ranges.

The toxins indirectly act on the voluntary muscles as they actually target the motor nerve endings, and attack the active part of the protein. These nerve endings then emit a reduced signal to the muscle. “It [botulinum toxin] goes into the nerve endings… and it’s like a pair of

In closing, Dr. Samanta stressed the importance of the following for successful results with botulinum toxin treatments:

• Injection sites are important.

• Physician’s experience matters.

• Starting low and gradually increasing doses is advised.

• Patient Feedback, especially in the results and side-effects experienced, are very important to communicate with your treating physician.

• Cosmetic Botox is still Botox. Having it performed between treatments can actually cause you to experience a build-up of resistance with reduced treatment effectiveness.

* Research partially funded by BEBRF

BLEPHAROSPASM AND BOTULINUM TOXIN

► Common dosing ranges for blepharospasm treatment:

► Botox: 20-100 units (higher for Meige)

► Dysport: 80-240 units

► Xeomin: 25-100 units

► Myoblock: 400-2500 units

BEBRF ATTENDS THE OPTOMETRY ACADEMY

A few years ago, BEBRF began attending the Optometry Academy to create more awareness and familiarity of blepharospasm with optometrists. For many years, BEBRF had attended Ophthalmology and Neurology Academies, but not the academy for optometrists, who don’t typically ‘treat’ blepharospasm. However, if someone is having spasms in their eyelids, the first healthcare practitioner they are likely to see is the optometrist, so BEBRF started also attending their annual academy so that patients could get diagnosed and subsequently treated more quickly.

In October, 2022 BEBRF attended the American Academy of Optometry in San Diego, CA. The optometrists, and especially the optometry students, were very keen to learn more about blepharospasm. Attendees were from all over the world. Those who came to the BEBRF booth received a flash drive with a presentation by Dr. Laura Scorr of Emory University on the different types of facial movement disorders and how to tell them apart. Several booth visitors represented optometry schools in places like Nigeria and Belarus, and they received

numerous flash drives to share with their faculties in their home countries. Executive Director Charlene Hudgins visited every booth representing an optometry school and gave out more of the flash drives.

Several optometrist’s stated that they believed they had patients with blepharospasm and asked how BEBRF could help both the optometrist and the patient. BEBRF shared contact information, Newsletters, brochures, and more. Since the academy, several of those optometrists have contacted the BEBRF office and received even more help.

Exhibits 2.0 is a company that puts together really large exhibits for large pharmaceutical companies, and their President, Lou Crescenti, stopped by the BEBRF booth to learn more about our non-profit. He then donated the collapsible newsletter/brochure rack pictured. BEBRF extends heartfelt thanks to Mr. Crescenti and Exhibits 2.0.

The people who worked the booth over the three days of the academy included Charlene, Jane Boyd MD Vicepresident of Physician Outreach, Cynthis Clark – Western District Director, and Joanne Matuzas – California State Coordinator (not pictured).

OPPORTUNITIES TO PARTICIPATE IN RARE DISEASE DAY

Rare Disease Day is February 28th (February 29th in leap years), and this year there are two opportunities for patients to participate in meaningful activities. Registration links for these events are posted under the Events Calendar on the BEBRF Website.

The day before on February 27th, the Food and Drug Administration (FDA) of the US government will be holding a Virtual Event entitled “Intersections with Rare Diseases – A Patient-focused Event,” which will explore a range of topics related to rare diseases. Participants will have the opportunity to:

• Hear directly from the FDA on initiatives to advance medical product development for rare diseases.

• Engage with the FDA to provide your perspective as a patient, caregiver, or family member.

• Understand considerations and challenges associated with clinical trials in small populations.

• Hear from medical students on rare disease education for medical professionals.

On February 28th, the National Institutes of Health (NIH)’s National Center for Advancing Translational Sciences (NCATS) will co-sponsor this year’s Rare Disease Day event at the NIH Clinical Center.

This event aims to raise awareness about rare diseases, the people they affect, and NIH research collaborations that address scientific challenges and advance research for new treatments. This is a free event that is open to the public, including patients, patient advocates, health care providers, researchers, trainees, students, industry representatives, and government staff. This year’s event will be both virtual and in person at the Natcher Conference Center in Bethesda, MD. A livestream will be available via NIH VideoCast with the event archived for replay afterward.

2022 OUTSTANDING VOLUNTEER AWARD

At the Symposium in Phoenix, BEBRF was proud to present the 2022 Outstanding Volunteer Award to Peter Bakalor during the Friday night Meet & Greet.

Peter has volunteered for BEBRF for decades. He has served as Western District Director, Board Treasurer, and Medical Academy representative. He is currently serving on the Executive Committee of the Board of Directors as the Vice-President of Development, as well as continuing in his on-going role of Support Group Leader in the Seattle and greater northwestern United States. Peter was also instrumental in developing information technology for BEBRF.

Peter was very surprised to receive this award, and in his acceptance of it he thanked all the people he has worked with through his association with BEBRF. He finally declared that the Award would have “pride of place” in his home. BEBRF thanks Peter for his years of service to the Foundation and to helping other patients suffering from blepharospasm and its related disorders.

Peter Bakalor

LITTLE ROCK SUPPORT GROUP MEETING

SUPPORT GROUP MEETINGS

To get your support group meeting in the next issue of the newsletter, please notify the Foundation office, before April 1, 2023, the next newsletter deadline. If you are interested in attending an online meeting but are not currently in a location with a support group leader, please contact us, and we will try to find you a meeting.

EASTERN DISTRICT

Eastern District Meeting

For residents of the following states:

CT, DE, DC, FL, GA, MA, MD, ME, NH, NJ, NY, NC, PA, RI, SC, VT, VA, WV

Date: Thursday, February 16, 2023

Time: 2pm – 4pm Eastern Time

Location: Zoom (Please contact Bryan for invitation instructions to meeting.)

Contact Person: Bryan Renehan

Phone: 301-461-0679

Email: bryan.renehan@gmail.com

CENTRAL DISTRICT

Central District Meeting

For residents of the following states: AL, AR, IL, IN, IA, KS, KY, LA, MI, MN, MS, MO, ND, OH, SD, TN, TX, WI

Date: Wednesday, March 29, 2023

Time: 1pm-3pm eastern time

Location: Zoom

Please contact Tishana for invitation instructions to meeting.

Contact Person: Tishana

Phone: 606-303-1132

Email: tishana333@yahoo.com

West Dallas/Fort Worth, Texas

Date: Thursday, April 20, 2023

Time: Noon - 2pm Central Time

Location: Zoom (Please contact Sharon for invitation instructions to meeting.)

Contact Person: Sharon West

Phone: 817-297-4389

Email: swest124@swbell.net

NATIONAL/INTERNATIONAL SUPPORT

NATIONAL Support Group Meeting

For Cranial Dystonia and Meige

Date: Thursday, February 9, 2023

Time: 1pm - 3pm Central Time

Location: Zoom (Please contact Charlene for invitation instructions to meeting.)

Contact Person: Charlene Hudgins

Phone: 409-832-0788

Email: charlene@blepharospasm.org

NATIONAL Support Group Meeting

Date: Tuesday, February 21, 2023

Time: 1pm - 3pm Central Time

Location: Zoom (Please contact Charlene for invitation instructions to meeting.)

Contact Person: Charlene Hudgins

Phone: 409-832-0788

Email: charlene@blepharospasm.org

NATIONAL Support Group Meeting

Date: Thursday, March 23, 2023

Time: 1pm - 3pm Central Time

Location: Zoom (Please contact Charlene for invitation instructions to meeting.)

Contact Person: Charlene Hudgins

Phone: 409-832-0788

Email: charlene@blepharospasm.org

NATIONAL Support Group Meeting

Date: Friday, April 14, 2023

Time: 1pm - 3pm Central Time

Location: Zoom (Please contact Charlene for invitation instructions to meeting.)

Contact Person: Charlene Hudgins

Phone: 409-832-0788

Email: charlene@blepharospasm.org

IF YOU ARE INTERESTED IN LEARNING MORE ABOUT STARTING A SUPPORT GROUP, CONTACT THE BEBRF OFFICE AT 409-832-0788.

MORE BEBRF SUPPORT GROUP MEETING PHOTOS

NORTHEAST TEXAS SUPPORT GROUP MEETING

TARRANT

COUNTY SUPPORT GROUP MEETING

WASHINGTON, DC SUPPORT GROUP MEETING

NATIONAL SUPPORT GROUP MEETING • NOVEMBER, 2022

DALLAS/FORT WORTH SUPPORT GROUP MEETING

PARKER

It is our editorial policy to report on developments regarding BEB/Meige and related disorders, but we do not endorse any of the drugs or treatments in the Newsletter. We urge you to consult with your own physician about the procedures mentioned.

I t is our editorial polic y to repor t on developments regarding BEB/Meige and related disorders but do not endorse any of the drugs or treatments in the Newsletter We urge you to consult with your own physician about the procedures mentioned

bENIGN ESSENTIAL bLEPHAROSPASM

RESEARCH FOuNDATION, INC.

P.O. BOX 12468

BEAUMONT, TEXAS 77726-2468

409-832-0788

Dated Material Enclosed

Overview of Blepharospasm Risk Factors, Diagnosis, and Treatment

by Padma Mahant, MD

Botulinum Toxin: Injection Techniques and Toxin Choices

by Johan E. S. Samanta, MD

Oromandibular Dystonia and Meige Syndrome

by Virgilio Gerald H. Evidente, MD

Exploring Alternative Management for Blepharospasm and Related Conditions

by Indu Subramanian, MD

Dry Eyes and Photophobia by

Obada Subei, MD

Deep Brain Stimulation Surgery for Blepharospasm: What Do We Know?

by Francisco Ponce, MD

Question and Answer Sessions