Annual Meeting Highlights for 2006
An overview of important programs and trial updates presented at the American Academy of Neurology and the Consortium of Multiple Sclerosis Centers' Annual Meetings
By Susan Wells Courtney
Reviewed by Jack Burks, MD
Each year, professionals specializing in MS diagnosis, care, and research, gather to exchange the latest in MS information at a number of important conferences, taking place both nationally as well as internationally. These meetings feature a variety of presentations, seminars, workshops, and poster sessions - all aimed at providing attendees with informative trial results and insightful treatment findings and recommendations. This article focuses on two of these meetings: the American Academy of Neurology's Annual Meeting and the Consortium of Multiple Sclerosis Centers' Annual Meeting.
In addition to the presentations and sessions, these two annual meetings feature an exhibitors' area, where many organizations and vendors set up booths to promote their cause, product, or service. MSAA participates in exhibit areas at both conferences to increase awareness of the organization and its mission, as well as to inform neurologists and other health professionals of the programs and services MSAA provides.
The first of these two conferences to take place was the American Academy of Neurology's (AAN) Annual Meeting, which was held in early April of this year in San Diego, California. This was the AAN's 58th Annual Meeting, and in addition to multiple sclerosis, topics included virtually all neurological diseases and conditions. Thousands of physicians, researchers, and other medical professionals traveled from all over the world to attend this week-long event.
The second conference was the Consortium of Multiple Sclerosis Centers' (CMSC) 20th Annual Meeting. This took place from May 31st through June 3rd in Scottsdale, Arizona. The CMSC is the "largest professional multi-disciplinary MS organization in the world," and was joined by the Latin American Committee for Treatment and Research in MS (LACTRIMS) as well as the International Organization of MS Nurses (IOMSN) in conducting this meeting.
To follow is an overview of some of the important information presented at these meetings. Information provided has been obtained from literature made available through the conferences. Both meetings present a tremendous amount of information, so only a few specific programs could be highlighted in this article. An overview of some of the clinical trial findings, which were presented in abstracts at both meetings, will appear in the Fall 2006 issue of The Motivator, in the Research News column.
Anyone wishing additional information on the AAN may visit www.aan.com. For information on the CMSC as well as abstracts and presentations from the meeting, readers may go to www.mscare.org.
American Academy of Neurology's 58th Annual Meeting
The AAN's Annual Meeting featured several sessions on the research and treatment of MS. Of particular interest to the MS community was this year's full-day course, "Update on Multiple Sclerosis." Among others, topics included: MS pathology, MRI imaging and lesions, diagnosis, and disease-modifying therapies. These sessions were presented by a faculty of top MS specialists. To follow is a brief overview of these different presentations.
Pathological Insights and Their Clinical Relevance
Presented by Claudia Lucchinetti, MD, of the Mayo Clinic College of Medicine, this session looked at the pathology of MS, and how our understanding of the disease is changing. "Pathology" may be defined as the structural and functional changes within the body that cause or are caused by a disease.
Dr. Lucchinetti notes that MS has traditionally been viewed as an autoimmune disease, where T-cells specifically aimed at damaging one's own myelin cause an inflammatory process. Myelin is the protective covering to the nerves of the central nervous system (CNS), which is comprised of the brain and spinal cord. Additional attacking cells (known as macrophages) are "recruited," resulting in the destruction of myelin in areas along the nerves. According to Dr. Lucchinetti, the processes involved with MS may be more complicated than originally thought.
She goes on to state that the features which distinguish the relapsing-remitting type of MS versus the progressive disease course are not well defined. The fact that MS patients have varied responses to the long-term treatments for MS, may be indicative of genetic, clinical (symptomatic), or pathologic (disease course) differences among the patients.
Recent studies suggest that the different disease processes occurring with MS may be unique in subgroups of patients. These processes include: patterns of inflammation; damage to myelin, oligodendrocytes (the cells that build myelin), and nerves (also known as "axons"); as well as the ability to regenerate or repair myelin (a process known as "remyelination").
Four distinct patterns of these disease processes have been observed in MS patients - and no patient exhibits more than one type of pattern. These findings suggest the possibility that different therapeutic strategies may be beneficial in treating individuals with different patterns of MS.
Present MS therapies target the MS lesion by modulating inflammation. Dr. Lucchinetti points out that future therapy will require novel approaches aimed at limiting or preventing damage to myelin, nerves, and other targets, while promoting repair of these same targets which may have been damaged earlier.
Imaging and Multiple Sclerosis: Beyond the Lesion
This presentation was given by Nancy L. Sicotte, MD, of the David Geffen School of Medicine at UCLA. According to Dr. Sicotte, the MRI plays an important role in MS research, treatment, and insight into MS pathophysiology. "MS pathophysiology" may be defined as the basic processes underlying the disordered functions caused by MS.
Dr. Sicotte lists four examples of how the MRI has impacted MS research, diagnosis, and treatment. These are as follows:
(1) At the time an individual experiences initial symptoms, an MRI will usually show several areas of "signal abnormality" within the brain, indicating that affected nerves are malfunctioning. This finding suggests that for individuals with MS, changes occur in the brain prior to any symptoms. Changes occurring prior to the appearance of symptoms are referred to as "subclinical."
(2) Serial MRI scans (repeated scans at regular intervals) show that areas of new lesions develop without any new or worsening symptoms. This provides evidence that MS disease activity can be ongoing without any changes in symptoms.
(3) An MRI can establish dissemination of lesions in terms of time and space. This important observation enables physicians to diagnose MS earlier and prescribe a treatment sooner.
(4) A patient's response to a drug therapy may also be monitored through the use of an MRI. Specific MRI guidelines indicating how to determine the degree of treatment effectiveness, however, are still being developed.
One problem is that lesions, as seen on conventional MRI scans, only modestly correlate with one's degree of disability and prognosis. Dr. Sicotte suggests that this is due to the non-specific nature of these images, which may represent edema (swelling), myelin damage, myelin repair, scarring, or nerve loss. Given this uncertainty, researchers continue to search for better, non-conventional MRI techniques. Examples of such techniques include magnetization transfer imaging (MTI), spectroscopy, and functional imaging.
Consortium of MS Centers' MRI Protocol for Diagnosis and Follow-up of MS
This listing of recommendations and instructions for using MRI scans of the brain and spinal cord in the diagnosis and follow-up of MS, was developed by a group of MS experts in June 2003.
This report first provides clinical guidelines for MRI in MS, detailing when MRI scans are recommended in instances of suspected MS, as well as after diagnosis for follow-up evaluation. MRI protocols are also given, stating recommended: magnetic field strength; thickness of each area scanned, scan orientation, and coverage; sequences for brain MRI and spinal cord MRI; and administering gadolinium (substance that enhances the appearance of lesions). The guidelines also include time-saving strategies and details what an MRI report should include.
These types of guidelines are crucial to the long-term care and follow-up of patients. When doctors follow these specific clinical guidelines, a consistency is achieved that allows for accurate comparison of findings over time and between different medical facilities.
Diagnostic Criteria for MS: Application and Pitfalls
Brian G. Weinshenker, MD, FRCP(C), of the Mayo Clinic College of Medicine, gave this presentation which follows the diagnostic criteria since 1954, when the first set of "diagnostic criteria for MS" was proposed. Dr. Weinshenker notes that diagnostic criteria have undergone many updates, largely as a result of advances in technology (particularly spinal-fluid analysis and MRI).
Despite the changes made to each update, the basic principles for an MS diagnosis have remained the same. These include:
- Lesions disseminated in time and space, affecting predominantly white matter (portions of the brain tissue)
- Objective abnormalities (observed symptoms) on examination, preferably demonstrated at time of diagnosis
- Relapsing course (lasting at least one day and separated by at least one month) or progressive course (with continuous worsening for at least six months)
- No other diagnosis that might better explain the symptoms
- The diagnosis of MS remains tentative and could be modified as additional clinical evidence arises
He concludes by noting that while the diagnostic criteria have been of great value, they will need to be even more specific in the future. This specificity is necessary to better distinguish between the different demyelinating disorders, as well as to identify the different types and subtypes of MS. Dr. Weinshenker mentions that other diagnostic modalities, including serology (studies of immune reactions in the lab), may eventually be integrated into diagnostic criteria for earlier and more specific diagnosis.
Current Therapeutic Decision-Making in Multiple Sclerosis
Dean M. Wingerchuk, MD, MSc, FRCPC of the Mayo Clinic College of Medicine, gave an extensive overview of several aspects of MS therapy, along with the clinical trial data supporting these treatments. To follow is a greatly shortened overview of some of the main points presented by Dr. Wingerchuk.
Treatment of acute exacerbations
Clinical bottom line for treatment: short courses of corticosteroids to speed recovery from attacks, and plasma exchange for severe attacks that do not respond to corticosteroid treatment.
Treatment data: a meta-analysis (which is an overall evaluation of all trials conducted on a particular treatment) found that methylprednisolone given intravenously (injected directly into the blood system) was more effective than ACTH, and five consecutive days of administration worked just as well as 15 days; the effectiveness of oral prednisone for relapses has not been established; very severe exacerbations that do not respond to corticosteroids may respond to plasmapheresis; studies showed that intravenous methylprednisolone worked just as well alone versus being combined with intravenous immune globulin (IVIG); a single dose of natalizumab (Tysabri®) did not speed recovery from acute exacerbations, but did reduce lesion volume; and no treatment approach has been shown to improve long-term recovery from an exacerbation.
Clinically Isolated Syndromes (CIS)
Description: relapsing-remitting MS begins clinically with a flare-up of neurological dysfunction, often with a single event (known as a clinically isolated syndrome) - such as optic neuritis. Most patients have a second exacerbation, or new brain MRI lesions, within the following 18 months. At this time, patients often meet the criteria of having "clinically definite" MS.
Clinical bottom line for treatment: interferon beta-1a (Avonex®, Rebif®) delays the conversion to clinically definite MS and slows the extent of brain atrophy (brain-cell damage); new data suggests that interferon beta-1b (Betaseron®) may have similar effects; researchers do not know if these early benefits will affect long-term disease progression.
Treatment data: early treatment of a clinically isolated syndrome (CIS) is supported by: the CHAMPS and CHAMPIONS studies (Avonex); the ETOMS study (Rebif); and the BENEFIT study (Betaseron), which has been completed but published only in abstract form as of the date of the presentation. A small trial showed IVIG (large initial dose followed by small boosters every six weeks for one year) was also effective in reducing the probability of developing MS within a certain time frame, but further studies are needed. No studies using glatiramer acetate (Copaxone®) for CIS have been completed, but one study is underway (PreCISe study).
Relapsing-Remitting MS (RRMS)
Clinical bottom line for treatment: the interferons (Avonex, Betaseron, and Rebif) generally reduce relapse frequency by about one-third and reduce relapse severity, while modestly slowing disease progression; Copaxone reduces relapse frequency by about one-third but has not been demonstrated to reduce disability progression; Tysabri reduces attack frequency by two-thirds and reduces disability progression (by 42 percent at year two compared to placebo), but has only recently returned to the marketplace after three cases of an often-fatal brain disorder occurred (please see page 32 for more information on Tysabri's return); and mitoxantrone (Novantrone®) reduces relapse rate and the rate of disability progression for patients with worsening relapsing-remitting and secondary-progressive types of MS, although Novantrone carries significant risks (cardiotoxicity and leukemia).
Editor's note: The results of trials vary significantly according to the patients who participated; given the fact that none of these trials were conducted "head-to-head," where the different drugs are directly tested against one another. Comparing drugs which were studied in separate trials may not always be an accurate measure to determine which drug may be superior. Please note that several head-to-head studies are in progress or were recently completed; these include the BEYOND study (Betaseron versus double-dose Betaseron versus Copaxone), as well as a Rebif versus Copaxone study.
Treatment data: individual studies (and meta-analyses of published trials with interferons and Copaxone) support the findings listed; the INCOMIN and EVIDENCE studies show some evidence of a dose-effect (greater doses promote a greater response), with Betaseron and Rebif each compared to Avonex. Long-term follow-up studies have been conducted with the interferons and Copaxone, although objectivity can sometimes be difficult with these types of unblinded, extension follow-up studies. Tysabri was supported through the AFFIRM and SENTINEL studies, while Novantrone's data was derived from a two-year trial.
Secondary-Progressive MS (SPMS)
Clinical bottom line for treatment: results of interferon trials for SPMS were mixed; Betaseron showed modest slowing of disease progression, but most likely in patients who continue to have clinical flare-ups; Avonex slowed SPMS progression as measured by one scale (the Multiple Sclerosis Functional Composite), but progression measured by the more commonly used EDSS (Expanded Disability Status Scale) was unaffected. No data supports a role for Copaxone in treatment of SPMS. Novantrone showed a dose-related (higher dose, higher response) treatment effect with "recent rapid worsening" cases of RRMS or SPMS, but the trial was small and had a high dropout rate; many combination studies using Novantrone with other drug therapies are ongoing or planned. A trial using IVIG therapy for SPMS did not succeed in reducing the rate of progression.
Neutralizing Antibodies
Treatment with interferons commonly induces binding antibodies. Because of their effects on the drug in the lab, these are known as "neutralizing antibodies," and are frequently referred to as "NAbs." The clinical importance of NAbs is not completely understood.
Recent observations have found that: patients usually develop NAbs between six to 24 months after starting interferon treatment; individuals who do not develop NAbs for the first 24 months will most likely not develop them; individuals who continue to be NAb-positive for 18 months will most likely remain NAb-positive.
Dr. Wingerchuk notes that some studies support a negative effect of NAbs on disability progression (with NAb-positive patients showing an increase in EDSS scores versus NAb-negative patients). Strategies to prevent or eliminate NAbs are controversial, and researchers do not know if switching to another dose or long-term treatment will improve the clinical outcome. Additionally, some NAb-positive patients remain in remission.
Editor's note: The AAN's position is that the data on NAbs are too conflicting and/or confusing to make specific recommendations. The ANN is re-reviewing its position on NAbs, and MSAA will publish the outcome when it becomes available.
Copaxone also induces "reactive antibodies," but conclusions are mixed regarding their biological effects. Studies regarding antibodies with both the interferons and Copaxone are expected to continue.
Consortium of Multiple Sclerosis Centers' 20th Annual Meeting
Using the theme, "Celebrating 20 Years of Excellence in MS Care and Research," the Consortium of Multiple Sclerosis Centers' (CMSC) Annual Meeting covered an enormous amount of information presented by an extensive faculty of MS experts, from researchers, physicians, and nurses, to physical therapists, social workers, and others. During the four-day conference, medical professionals attended educational events which included information on: MS research, diagnosis, and disease-modifying treatment; treatments for symptoms and MS-related issues; and other areas of care and support (such as nursing, patient perspectives, and overall health).
The previous section covering the AAN's Annual Meeting highlighted topics that addressed MS research, diagnosis, and treatments. With this in mind, different topics from the CMSC conference are featured. To follow are brief overviews of: (1) the MS Coalition's Dinner and Workshop; (2) the Heuga Center Approach to Overall Health Promotion (on the importance of physical activity), and (3) Pediatric MS: Perceptions of MS in Children and Teens.
The MS Coalition's Dinner and Workshop
The MS Coalition hosted a welcoming dinner and a separate workshop at the CMSC's Annual Meeting. The founding members of the MS Coalition are the Multiple Sclerosis Association of America (MSAA), the Multiple Sclerosis Foundation (MSF), as well as the Consortium of Multiple Sclerosis Centers (CMSC). During the dinner, all three organizations presented brief overviews of the background to the MS Coalition and the opportunities for better services to MS patients through greater collaboration.
Of particular note was the presence and participation of Joyce Nelson from the National Multiple Sclerosis Society (NMSS), who expressed her willingness to work with the MS Coalition to better serve the respective MS constituencies. A follow-up organizational meeting has been scheduled to build on this potential partnership and determine how these organizations can effectively work together.
The MS Coalition's Workshop entitled "MS Coalition Resources - A Hands-on Approach" was held to clearly define programs and resources available through the MS Coalition and its three founding organizations. Healthcare professionals attended the workshop to learn about all the programs offered through the different member organizations as well as the program application process. The Coalition hopes to expand the network in an effort to address some of the unique challenges faced by organizations providing services to those affected by MS. In addition, the MS Coalition seeks to collaborate on educational programs and advocacy, with the ultimate goal of improving the quality of life for those affected by MS.
The Heuga Center Approach to Overall Health Promotion
One of the three topics discussed in this presentation, given by Brian Hutchinson, PT, MSCS, of The Heuga Center, was "The Importance of Physical Activity in Managing People with MS." To follow is a brief summary.
The effects of MS on exercise include: primary effects (blunted blood pressure responses, a decrease in autonomic cardio-vascular functions, and fatigue); secondary effects (impairments, including issues with range of motion, weakness, sensation, balance/coordination, fatigue due to de-conditioning, pain, side effects from medications, mobility, and cognition); and tertiary effects (emotional and accessibility issues).
Studies show that exercise has positive effects on MS. With exercise, participants were found to experience improvements in range of motion, strength, endurance, fatigue, pain, balance/coordination, bowel and bladder function, and activities of daily living. Participants also experienced improvements in their quality of life, through improved emotional behavior, social interaction, recreation, and home management, along with a reduction in depression and anger. Improvements were observed in physical health measures as well, affecting the volume of oxygen consumed while exercising (VO2 max); and reducing body fat and blood lipids. Additionally, a 16-week program of resistance exercise demonstrated (among other positive changes) a decrease in pro-inflammatory cytokines and an increase in anti-inflammatory components within the immune system of participants (University of Buffalo, 2002).
Readers should note that moderate exercise appears to reduce one's susceptibility to infections, while exhaustive exercise might enhance inflammation. The presenter concluded by noting the importance of a physical activity program for individuals with MS. Such programs need to be monitored by a healthcare professional who specializes in exercise and rehabilitation management for people with MS.
Pediatric MS: Perceptions of MS in Children and Teens
This program was presented by Jennifer Boyd, RN, MHSc, MSCN, who is a Clinical Nurse Specialist with the Pediatric Multiple Sclerosis Clinic at the Hospital for Sick Children. The information provided is taken directly from the presentation materials.
When children learn of their MS diagnosis, they feel scared, sad, and worried. They can experience confusion and sometimes relief. They may think the worst, that they will die, or they may think that the MS will go away. Their understanding of the disease is limited, and they typically don't remember the details.
Just as adults, children with MS are frightened about the unpredictability of relapses; they feel uncertain about the future and the impact MS will have on their life. They are frustrated with symptoms and feel sorry for themselves, even depressed. They want to be cured; they don't take life for granted.
Keeping things the same as they were before MS came along is important for children with MS. They need to continue with the same activities (school, friends, sports, activities, etc.). Children will still have the same emotions and personality as they did prior to their diagnosis.
Dealing with MS creates many stressors, including (among others) the unpredictability of symptoms and relapses, restrictions on lifestyle, the challenges of a treatment regimen, and days missed from school. Children may use coping strategies, such as maintaining a positive outlook, striving for goals and dreams, identifying positive role models, seeking support, and accepting treatment, to name a few. Negative coping strategies include denial, avoidance, manipulation, getting involved in distractions (such as smoking marijuana), and hiding their differences (symptoms and treatments) from others.
The presenter concluded by providing advice to children diagnosed with MS.
Some of the key points include: remain positive, keep fighting, and believe in oneself; remember that people don't die from MS; make changes to decrease stress and fatigue; and be more cautious. Additionally, MS involves needles, tests, and uncertainty, so involve others who can help.
Additional Notes
The information provided in this article from these two annual meetings is representative of just a small fraction of what was made available to the medical professionals who attended. Researchers, neurologists, and other MS specialists have gathered a tremendous amount of information, all aimed at promoting a better understanding of MS and improving treatment options.
As members of the MS community look to the future, they may be assured that new findings in MS research as well as innovative treatments will continue to be discovered. When such information becomes available, medical professionals know that it will often be initially presented and discussed at medical conferences, which is why the annual meetings of the AAN and CMSC (among others) are so important to the care and outlook of individuals with MS.
