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foreSIGHT Newsletter, Summer 2004 Neuromuscular Retraining and Botax Neuromuscular Retraining and Botox: powerful pair in treating
facial paralysis Singing, speaking, smiling and closing her eyes – these are some of the movements controlled by facial muscles that Casey Niesen took for granted before she was affected by facial paralysis. “The face is the mirror of the soul,” says the now 60-year-old Green Bay resident who developed Bell’s Palsy, a condition in which damage to the facial nerve occurs, when she was 50. “It was devastating not to be able to reveal my emotions and feelings through my face,” says Niesen, who enjoyed singing and performing publicly for most of her life. The initial paralysis affected Niesen’s speech and made it difficult for her to form the consonants “p” and “f”. “The right side of my face felt heavy and tense,” explains Niesen. “I couldn’t completely close my right eye for nine months.” Niesen was one of approximately 15 percent of those who don’t recover from Bell’s Palsy, which afflicts about 40,000 Americans each year. Within a few months of being diagnosed, she would go on to develop synkinesis, which is the abnormal contraction of one muscle when a different muscle is voluntarily contracted. This condition, due to abnormal healing of the facial nerve, would make nonverbal communication like smiling a challenge for the former teacher. On the recommendation of someone from Green Bay who had been treated for Bell’s Palsy previously, Niesen sought help from UW Health facial retraining specialist, Jackie Diels, OT, in Madison . “I was desperate,” recalls Niesen, who at that time found her mouth pulled downward when she tried to smile. “If it wasn’t for Jackie’s empathy and listening skills, I wouldn’t have gotten through it.” Diels says most new patients don’t have any idea how their facial muscles work. “If the wrong muscle pulls, you get the wrong facial expression,” explains Diels. “It’s like stepping on the brakes in your car and having your windshield wipers come on.” Diels says her job is to help the patient re-learn how to create the appropriate expression. “I have a patient look in the mirror while I help to walk him/her through the movements to bring about the desired expression,” the therapist says. “It’s about helping the patient relax the muscles that are overworking due to the synkinesis.” “The first time I worked with Jackie, I moved the right corner of my mouth a little bit with her instructions,” says Niesen. ”I cried. It was the first time anything had moved on the right side of my face in months.” In addition to recommending specific daily facial exercises, Diels suggested that Niesen consider seeing an oculoplastic specialist for botulinum toxin Type A (Botox) injections to relax her overactive facial muscles. “Although it’s not a cure,” says UW Health oculoplastic specialist, Mark Lucarelli, MD, “Botox has been used effectively to help patients like Casey who have synkinesis from Bell’s Palsy, or other muscle disorders from conditions such as acoustic neuroma, shingles or traumatic injury. Botox temporarily paralyzes abnormal muscle contractions and improves muscle movement patterns,” Dr. Lucarelli says. “When the drug is used in conjunction with neuromuscular re-training, a patient doesn’t have to work as hard to achieve the desired expression.” Dr. Lucarelli, Jackie Diels and former UW ophthalmology resident Sonja Wamsley, MD, MPH, presented a paper detailing their work with neuromuscular retraining and Botox injections at the Association for Vision in Research and Ophthalmology (ARVO) conference in 2001 and the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) meeting in 2002. “Many of the facial paralysis patients I see have been told that nothing could be done to help them,” Dr. Lucarelli explains. “The purpose of our presentation was to make physicians more aware of the benefits of neuro-muscular retraining and Botox injections for people suffering from facial paralysis.” Dr. Lucarelli says a number of patients reported that Botox offered them “a window of opportunity to be relieved of abnormal contraction of a particular facial muscle while they practiced techniques of inhibiting other problem muscles.” Casey Niesen has been taking advantage of that “window of opportunity” three times a year for the past nine years. Prior to her Botox injections, Niesen visits Diels for a facial muscle evaluation. Niesen then receives her injections from Dr. Lucarelli at the University Station Clinic in Madison . During her treatment in April 2004, Dr. Lucarelli injected three of Niesen’s facial muscles: the platysma (neck), mentalis (chin) and orbicularis oculi (eye) because of contractions in these muscle areas. The right side of Niesen’s face is more relaxed now; she can form her sounds and her eye doesn’t contract each time she smiles. She can also smile – but it’s not a full smile like before the Bell’s palsy. “I feel confident with Dr. Lucarelli’s care, and I would certainly recommend this treatment to other people with this problem,” says Niesen. “This is one thing that I’ve done that gives some comfort and relief from the effects of abnormal muscle contractions.” After nine years of traveling to the Madison clinics, Niesen says she will continue to make the trip to see Diels and Dr. Lucarelli. “Jackie and Dr. Lucarelli are a good team – they work hand-in-hand to provide the best treatment for my individual situation,” Niesen says. Her treatment has allowed Niesen to continue singing – but not in solo roles in musicals or plays where all eyes would be on her. “I’m still not able to show full emotion,” she says. However, she does sing masterpieces with the 150-member Dudley Birder Chorale, an audition-only group in Green Bay that performs at St. Norbert College in De Pere and the Weidner Center in Green Bay . “My appearance is much better and my face is more relaxed since the Botox injections,” Niesen says. “I feel grateful about how far I’ve come.” From the Chair Research, patient care and education are the cornerstones upon which our department was built. We were pleased to learn that in 2003, the UW Department of Ophthalmology and Visual Sciences was ranked second in the amount of research funding provided to ophthalmology departments in U.S. medical schools from the National Institutes of Health. These rankings, released in May, provide a quantitative measure of the excellence of our department’s research team. Speaking of quantitative measures, I have now had the privilege of serving the department as interim chair for over a year and a half. We continue to press forward in seeking an outstanding person to become the permanent chair. The research article in this issue of foresight exemplifies why we have reached such preeminence in research. UW Associate Professor Arthur Polans, PhD, has been researching ocular cancers and has recently integrated “laser capture” techniques into his lab. Since its introduction in the 1950s, laser technology has made an enormous impact in fields such as engineering, communications and medicine. The precision of laser energy, coupled with specially-designed plastics, now allows scientists to select and remove individual cells from human tissue specimens on a glass slide. Pair this with molecular and genetic techniques that have been developed in the last decade, and the doors open for new possibilities in identifying the characteristics of cancer cells and their metastases and bring hope to patients who face this difficult disease. In our patient care story, you’ll learn that Botox isn’t just for cosmetic purposes. Before it became widely known as a treatment for cosmetic concerns like frown lines, the FDA approved Botox for neurological and eye muscle disorders related to muscle spasms. UW oculoplastic specialist, Mark Lucarelli, MD, has been a pioneer in helping patients with facial paralysis through an innovative combination therapy of Botox plus neuromuscular re-training. The story of one patient’s struggles in overcoming Bell’s Palsy is featured on this edition’s cover. Medical science depends on new discoveries to move forward. In this issue of foresight, innovative advances that impact both patient care and translational research are highlighted. I hope you enjoy learning about the exciting discoveries happening here. Education The Wisconsin Eye MD Spring Symposium will be held on May 7 and 8, 2004. This year’s event will be held at the Grand Geneva Resort in Lake Geneva, Wisconsin. This annual conference is held in collaboration with the Wisconsin Academy of Ophthalmology and the Medical College of Wisconsin, Department of Ophthalmology. Special guest lecturers will include Joan Miller, MD, from Massachusetts Eye and Ear Infirmary as the Alice R. McPherson lecturer, and Peter McDonnell, MD, from Wilmer Eye Institute as the George K. Kambara lecturer. Current Concepts in Eye Care, an all-day continuing education program for optometrists, was held on September 6, 2003. Education was presented in Grand Rounds format by 12 UW ophthalmologists to 77 optometrists in practices throughout Wisconsin. Topics included diabetic retinopathy, cosmetic Botox, cataracts, glaucoma, ocular hyperten Public Events Macular Degeneration: Progress in Sight IV, one of the largest macular degeneration symposiums in the country, will take place April 7, 2004 at the Alliant Energy Center. This free educational event has hosted such keynote speakers as the former first lady Laurie McCallum and author Lylas Mogk, MD. The event will be sponsored by the UW Department of Ophthalmology and Visual Sciences and the Wisconsin Council of the Blind. Registration will open in February. Lions Eye Research Update Lasers have many ophthalmic uses, from sealing leaking blood vessels in macular degeneration to repairing retinal tears to refractive surgery, but lasers have important implications in the eye research laboratory as well. The laser now also offers research opportunities which may lead to new cancer treatment discoveries. Laser capture microdissection is a method for precisely lifting specific cells from microscopic regions of tissue affixed to a glass slide. Developed in the late 1990s, this new technology has been recently integrated into the laboratory of UW Ophthalmology and Visual Sciences Associate Professor Arthur Polans, PhD. Under the microcscope, tissues appear as a composite of different interlocking cell types. “Every cell type in our body has a particular function, related to the pattern of genes each cell expresses,” Dr. Polans explains. “With laser capture we can precisely select and remove a particular type of cell, whether it is a tumor cell or a retinal photo-receptor cell, from a complex tissue specimen and then perform studies on that one cell type to learn more about its function and the genes it expresses.” Historically, pathologists have used tissue specimens for histological (cell structures seen under a microscope) comparisons using general staining methods. But today, technological progress paired with advances in our understanding of molecular and genetic information allows these same specimens to be examined in a new and quantitative fashion. Even something as precise as the level of gene expression can be determined from just a few cells gathered by laser capture. The technique of capturing the cells involves placing a cap that looks somewhat like the plastic head of a clear thumbtack over the specimen affixed to the glass slide. One end of the cap is coated with a clear plastic film, and when the laser energy passes through the cap and onto the specimen, the targeted cells bind to the film and can be peeled away from the slide. The film is then placed into a solution that releases the cells’ contents for further study. Once the cells are captured, they are processed in a technique known as quantitative or real-time PCR (polymerase chain reaction). PCR helps amplify the number of copies of a particular message encoded by a gene in a precise manner that allows the level of gene expression in a particular cell to be determined. While this work in the laboratory sounds abstract, it has practical implications for human diseases. Dr. Polans’ laboratory has been studying specimens from patients with ocular melanoma who participated over the last 20 years in a National Institutes of Health (NIH) clinical trial called the Collaborative Ocular Melanoma Study (COMS). Many of these patients had an eye removed because of the presence of a tumor, and some patients also had biopsies taken from other tissues if the eye tumor metastasized to other locations. Dr. Polans notes, “We have a tremendous amount of information about these specimens – tumor site and size, cell type, vascular patterns and patient outcome, to name a few. We can now go back to the archived specimens and do correlative studies at the gene level and ask why some ocular melanoma cells are more malignant, how tumors metastasize, and how we might impact the treatment and prognosis of the disease.” Primary tumor cells from the eye can be compared with cells that form metastases in other tissues to learn more about the progression of the disease. Dr. Polans poses some of the key questions his lab explores. “Were the primary tumor and the meta-static tissues the same? Maybe the metastatic cells mutated further or altered their expression of certain genes in some way to enhance their migration to other sites or ensure their survival once they got there.” Mutations or gene expression patterns found in the metastatic cells that were absent in the primary eye tumor may indicate that those cells have gained a selective advantage worth studying further. Understand-ing these differences in mutations and gene expression could help determine which patients are at high risk of metastasis, and therefore need to be treated more aggressively. Some of the genes in tumor cells studied by Dr. Polans encode receptors that allow them to bind to naturally occurring elements, such as hormones, as well as with chemicals used in drug therapies. Identifying the presence and levels of such receptors helps scientists to develop improved drug therapies to treat specific tumor cell types. Deciphering the cell pathways activated by these receptors might also help to create drugs that induce tumor cell death in a targeted fashion, and not just in the eye. “Our laboratory has extended its molecular pathology studies beyond eye tumors,” Dr. Polans says. “We are now investigating certain genes and receptors for the top ten pediatric and adult cancers, including neuro-blastoma, breast and lung cancer, to learn about how cancerous cells work and respond to new drugs.” Improved drug design, in turn, depends on understanding how molecules interact. A new technol-ogy, known as SPR (surface plasmon resonance) spectroscopy, can be used to study molecular interactions in cancer cells and bridges biochemistry and chemical engineering. A molecule to be studied is first anchored to dextran (a type of sugar compound) which is then attached to gold foil chips. A light is passed through a prism onto the chip, and is reflected at a particular angle. Potentially interacting molecules are then passed across the chip, and if they bind to the dextran-immobilized molecule, the angle of light reflection is changed. “Once identified, the amino acids compromising the interacting protein can be changed in the lab and then passed over the anchored molecule again,” Dr. Polans says. “This helps specify the sites of interaction between the two molecules. These are the sites that we then pursue in drug development, either to block or enhance their interaction and thereby selectively interfere with the growth, migration or survival of tumor cells.” “Translational science involves identifying a disease, taking it to the laboratory and learning as much as we can about its molecular, genetic, and biochemical features,” Dr. Polans explains. “Based on that information, we can then develop drugs which interfere in the progression of the disease, trying them in animals, then taking the solutions back to the patient. Laser capture, real-time PCR, and SPR are new techniques that accelerate the transfer of findings from the lab to the patient,” he says. “And ‘bedside to bench to bedside’ is what translational science is all about.” |
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