MS

<body topmargin=0 leftmargin=0 marginheight=0 marginwidth=0> <table cellpadding=0 cellspacing=0 border=0 height="100%"><tr> <td valign="top" width=210 BGCOLOR="#FFFFFF" TEXT="#080000" bgproperties="fixed" background="112f2f02egerdp.jpg"> <div> <A HREF="index.htm" TARGET="_top" TITLE="_"><U><B>RETURN TO HOMEPAGE</B></U></A></div> <div> <TABLE BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="195" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="LEFT" HSPACE="0" VSPACE="0" BGCOLOR=#FFFFFF > <tR> <tD VALIGN=TOP BGCOLOR=#66FFFF HEIGHT= 23 WIDTH="195"><div> <B> </B><A HREF="id91.htm" TARGET="_top" TITLE="BRUCE ROSEMAN, M.D. 330 West 58th Stree"><U><B>CONTACT ME</B></U></A></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFCC99 HEIGHT= 23 WIDTH="195"><div> <B> </B><A HREF="id17.htm" TARGET="_top" TITLE="office info"><U><B>OFFICE INFO</B></U></A></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFF99 HEIGHT= 23 WIDTH="195"><div> <B> </B><A HREF="id116.htm" 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ALIGN="bottom" WIDTH="195" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <bR> </td> <td valign="top" BGCOLOR="#FFFFFF" TEXT="#080000" bgproperties="fixed" background="115f0f03.jpg"> <div> <I>MS</I></div> <div> <A HREF="#multiple_sclerosis" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Multiple Sclerosis Questions and Answers</U></A></div> <div> <A HREF="#advances_in_multiple_sclerosis_research_" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Advances in Multiple Sclerosis Research and Treatment: Posted 05/10/2004</U></A></div> <div> <A HREF="id47_decade_long_benign_ms_predicts.htm" TARGET="_top" TITLE="HANDOUTS "><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Decade-Long "Benign" MS Predicts Continuing Stable Disease</U></A></div> <div> <A HREF="id47_cholesterol_drugs_promising_in_multiple.htm" TARGET="_top" TITLE="HANDOUTS "><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cholesterol Drugs Promising in Multiple Sclerosis</U></A></div> <div> <A HREF="#therapy_slows_down_multiple_sclerosis" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">immunoglobulin therapy applied after the first signs of MS significantly reduced the probability of developing clinically definite multiple sclerosis.</U></A></div> <div> <A HREF="#discovery_science_meets_multiple" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Discovery Science Meets Multiple Sclerosis</U></A> 11/17/04</div> <div> <A HREF="#calabresi_article" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Diagnosis and Management of Multiple Sclerosis</U></A></div> <div> <A HREF="#calabresi_article" TITLE="MS"><U><I> </I></U></A><A HREF="#calabresi_article" TITLE="MS"><U><I>PETER A. CALABRESI, M.D., </I></U></A><A HREF="#calabresi_article" TITLE="MS"><U><I>Johns Hopkins University School of Medicine, Baltimore, Maryland 11/15/04</I></U></A></div> <div> <A HREF="#calabresi_article" TITLE="MS"><U><I>Note from Dr. Roseman-this is a beautifully written, illlustrated and informative article</I></U></A></div> <div> <A HREF="#patients_with_multiple_sclerosis_may" TITLE="MS"><U><I><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">"Patients with Multiple Sclerosis May Want to Take Wait-And-See Approach to Medications"</I></U></A></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">FDA approves new drug for treating  MS  12/14/2004    </U><FONT SIZE="3" COLOR="#FF0066" FACE="Arial" >  natalizumab, which will be marketed as Tysabri,</FONT></div> <div> <A HREF="#new_test_for_ms" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">New Test for MS</U></A></div> <div> <A HREF="#aspirin_for_fatigue_in_ms" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700dc99006600.png" HEIGHT="15" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ASPIRIN FOR FATIGUE IN MS</U></A></div> <div> <A HREF="#copaxone_" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Copaxone</U></A></div> <div> <A HREF="#not_all_interferon_beta_treatments_are" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Not all Interferon-beta Treatments are Created Equal in Developing Neutralizing Antibodies</U></A></div> <div> <A HREF="#vitamin_b12_demyelination" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Vitamin B12, demyelination, remyelination and repair in multiple sclerosis</U></A>.</div> <div> <A HREF="#mitoxantrone_effective_and_well" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mitoxantrone Effective and Well Tolerated for Treatment of Multiple Sclerosis in Daily Clinical Practice</U></A></div> <div> <A HREF="#tysabri_screening_news" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Tysabri Screening news</U></A></div> <div> <A HREF="#vitamin_b12_demyelination" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Vitamin B12, demyelination, remyelination and repair in multiple sclerosis.</U></A></div> <div> <A HREF="#leptin_blocking" TITLE="MS"><U><B><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </B></U></A><A HREF="#leptin_blocking" TITLE="MS"><U>LEPTIN BLOCKING</U></A></div> <div> <A HREF="#natalizumab_for_relapsing_multiple" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Natalizumab for Relapsing Multiple Sclerosis</U></A></div> <div> <A HREF="#nicotine_and_ms" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">NICOTINE AND MS</U></A></div> <div> <A HREF="#soy_based_inhibitor_holds_promise_as_ms" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Soy-Based Inhibitor Holds Promise as MS Treatment</U></A></div> <div> <A HREF="#vitamin_d_may_cut_multiple_sclerosis" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Vitamin D may cut multiple sclerosis</U></A></div> <div> <A HREF="#prolactin_may_ease_multiple_sclerosis" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Prolactin May Ease Multiple Sclerosis </U></A></div> <div> <A HREF="#estriol_for_ms_" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Estriol for MS?</U></A></div> <div> <A HREF="#ms_vaccine" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A vaccine designed to tackle multiple sclerois</U></A></div> <div> <A HREF="#ms_nerve_damage_repaired_in_lab_" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">a human antibody to re-grow myelin</U></A><A HREF="#ms_nerve_damage_repaired_in_lab_" TITLE="MS"><U> </U></A></div> <div> <A HREF="#blood_pressure_drug_hope_for_ms_" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Blood pressure drug hope for MS </U></A></div> <div> <A HREF="#effective_oral_medication_for_ms15___" TITLE="MS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">EFFECTIVE </U></A><A HREF="#effective_oral_medication_for_ms15___" TITLE="MS"><U><I>ORAL</I></U></A><A HREF="#effective_oral_medication_for_ms15___" TITLE="MS"><U> MEDICATION FOR MS   Fingolimod)(ORAL)</U></A></div> <bR> <bR> <bR> <bR> <bR> <div>  <A NAME="effective_oral_medication_for_ms15___"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A>EFFECTIVE <I>ORAL</I> MEDICATION FOR MS15    Dec 2008 </div> <div> Multiple Sclerosis - FTY720 (Fingolimod)(ORAL) Trial Results</div> <bR> <bR> <div> FTY720 (fingolimod), an experimental oral drug for relapsing MS is more effective than current treatments according to new research reported today. </div> <bR> <div> The trial, called TRANSFORMS, is the first of three studies of FTY720 to report. TRANSFORMS was a one year study involving 1,292 participants receiving either 0.5 mg or 1.25 mg FTY720 or interferon beta-1a (Avonex). </div> <bR> <div> During the study, people receiving interferon beta-1a experienced on average 0.33 relapses. People on the lower dose of FTY720 experienced 0.16 relapses (a reduction of 52%) and those on the higher dose 0.20 relapses (a 38% reduction). </div> <bR> <div> The study data is still being analysed and detailed results are planned to be presented at a conference in 2009. The manufacturers, Novartis, hope to submit the drug for licensing by the end of 2009. </div> <bR> <div> Pam Macfarlane, Chief Executive of the MS Trust said, "We welcome the positive results of the study. However, these are early results from a study looking at a short period of treatment. We look forward to the fuller results which we hope will give a clearer picture of the effectiveness of this drug for people with MS." </div> <bR> <bR> <bR> <div> <B><U> <A NAME="blood_pressure_drug_hope_for_ms_"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>Blood pressure drug hope for MS </U></B></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="164" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="160"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="160" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <B>A drug which has been used for decades to treat high blood pressure may turn out to be a key treatment for multiple sclerosis, say British researchers.</B> </div> <div> Amiloride was found to reduce degeneration of nerve tissue in mice and the team at Oxford University are now planning a trial in MS patients. </div> <div> It works by blocking the build up of high levels of calcium in nerve cells, which can lead to nerve damage. </div> <div> There are about 85,000 people with MS in the UK. </div> <div> The condition is caused by a defect in the body's immune system, which turns in on itself, and attacks the fatty myelin sheath which coats the nerves. </div> <div> This damage to nerve cells is caused in part by a build up of calcium. </div> <div> Professor Lars Fugger and colleagues investigated the effects of a specific channel, ASIC1, which controls the entry of calcium molecules into cells. </div> <div> In mice with a condition that mimics MS, they found that when the channel remains open, calcium can flood into nerve cells in higher than normal proportions and cause damage. </div> <div> Inflammation like that found in MS leads to acidic conditions, which would lead to the channel opening and too much calcium accumulating in nerve cells, Professor Fugger said. </div> <div> <B>Treatment</B> </div> <div> Amiloride, a drug used for many years to treat high blood pressure and heart failure, was found to stop calcium entering through the ASIC1 channel and prevent degeneration of nerve tissue in mice, the journal Nature Medicine reported. </div> <div> Professor Fugger from the Medical Research Council Human Immunology Unit said the fact the drug was already licensed would speed up the process of getting the treatment to patients should it be prove effective. </div> <div> He is currently working out what the appropriate dose would be in humans and plans to start a clinical trial next year. </div> <div> "To develop a drug from scratch takes 10-15 years and a billion dollars and some of them are abruptly halted by unexpected side effects," he said. </div> <div> "It was known that calcium is not good for nerve cells but it's not been appreciated how simple it is to block it." </div> <div> Dr Laura Bell, from the MS Society, said: "Protection of nerve fibres is a promising and vital area of research and this is why the MS Society is currently spending half a million pounds on a clinical trial investigating this type of nerve protection in people with MS. </div> <div> "The early stage results from Oxford are interesting and we look forward to seeing the findings of future studies." </div> <div> The research is published in Nature Medicine.</div> <bR> <div>  <A NAME="ms_nerve_damage_repaired_in_lab_"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A>MS nerve damage repaired in lab </div> <div> <B>US scientists have repaired the nerve damage caused by multiple sclerosis in lab experiments on mice. </B></div> <div> The team, from the Mayo Clinic in Rochester, hope their work will eventually lead to new treatments. </div> <div> MS is caused by a defect in the body's immune system, which turns in on itself, and attacks the fatty myelin sheath which coats the nerves. </div> <div> The researchers <B><U>used a human antibody to re-grow myelin</U></B> in mice with the progressive form of MS. </div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="624" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 75 WIDTH="2"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="75" ALIGN="bottom" WIDTH="2" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="615"><div> <B>The findings could eventually lead to new treatments that could limit permanent disability </B></div> <div> Dr Arthur Warrington </div> <div> Mayo Clinic </div> </tD> </tR> </TABLE></div> <div> They told a meeting of the American Neurological Association they hope to begin patient trials after perfecting the technique further in animal tests. </div> <div> MS affects around 85,000 people in the UK. Damage to the myelin coating undermines the ability of the nerves to work properly, leading to symptoms including blurred vision, loss of balance and, in some cases paralysis. </div> <div> Although the symptoms can be managed to some degree, there is currently no way to restore damaged myelin. </div> <div> <B>Kickstarts repair </B></div> <div> Researcher Dr Moses Rodriguez said: "The concept of using natural human antibodies to treat disease of this kind has not yet been tested in humans, but these research findings are very promising". </div> <div> His colleague Dr Arthur Warrington said: "The findings could eventually lead to new treatments that could limit permanent disability". </div> <div> Myelin repair normally occurs in the body spontaneously, but MS appears to sabotage this mechanism. </div> <div> The scientists found that a single low dose of the antibody - which was genetically engineered from a single cell - was enough to kick start it into action. </div> <div> However, they found that the remyelination process reached a plateau after five weeks. </div> <div> Tests also showed that the antibody worked even when combined with the steroid treatment which is often taken by people with MS. </div> <div> Helen Yates, of the MS Resource Centre, said the findings were "very good news". </div> <div> She said much emphasis in the research community had been placed on the search for a cure for the disease, but myelin repair could potentially help people regain previously lost function. </div> <div> Dr Laura Bell, of the MS Society, said: "Myelin repair is an exciting avenue of research that holds a lot of promise as an MS treatment. </div> <div> "This is an exciting study but it is early days - we'll be keen to see how it works in people with MS." </div> <div> Chris Jones, of the MS Trust, also stressed that the work was at a very early stage. </div> <bR> <div>  <A NAME="ms_vaccine"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A>MS vaccine handed safety boost <B>A vaccine designed to tackle multiple sclerois has passed initial safety tests, say Canadian scientists. </B></div> <div> It is hoped that the BHT-3009 jab might reduce the damaging immune system attacks which cause the disease. </div> <div> Early checks were carried out on 30 patients at Montreal Neurological Institute, reported the journal Archives of Neurology. </div> <div> A British expert said that the way was clear for bigger trials - perhaps showing real benefits to patients. </div> <div> There is no cure for MS, which happens when the body's own defence system launches an attack on the tissue that surrounds nerve fibres, causing irreversible and worsening symptoms such as weakness and vision loss. </div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="623" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 57 WIDTH="2"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="57" ALIGN="bottom" WIDTH="2" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="614"><div> <B>What this shows is that the DNA vaccine approach doesn't have any adverse consequences, but they will have to 'fine-tune' the vaccine further </B></div> <div> Professor Christopher Linington, University of Aberdeen </div> </tD> </tR> </TABLE></div> <div> DNA vaccines are already used in healthy patients to protect against infectious diseases, but the latest idea is to give them to patients with an existing disease such as MS. </div> <div> The Montreal researchers said they thought their study was the first time that a DNA vaccine had been given to someone with an "auto-immune" disease. </div> <div> Animal experiments have suggested that it might be possible to tweak the body's immune system so that the unwanted self-harming response becomes smaller, slowing the progress of the disease. </div> <div> <B>Scan secrets </B></div> <div> The small-scale Montreal trial - using 30 MS patients - was designed to check that the vaccine would not cause any unexpected side-effects in advance of large-scale trials. </div> <div> The scientists also checked to see if there was any evidence in the tiny number of patients who received the vaccine that it was having an effect on their disease. </div> <div> They found some differences in MRI scans of the brains of vaccine patients, and blood tests revealed a lower number of immune system cells targeting the proteins in the nerve fibre sheath. </div> <div> However, the trial was too small and too short to show whether, in the longer term, this might translate to a slowing of the illness or a reduction of symptoms. </div> <div> The researchers wrote: "We have demonstrated in this first, to our knowledge, in-human trial of a DNA vaccine for auto-immune disease that the approach is safe and well tolerated." </div> <div> Professor Christopher Linington, who researches the immunobiology of MS at the University of Aberdeen, said that the research was "exciting", and that to detect any evidence of benefits in such a small trial would have been "miraculous". </div> <div> He said: "What this shows is that the DNA vaccine approach doesn't have any adverse consequences, but they will have to 'fine-tune' the vaccine further to see if it will offer any benefits to patients." </div> <div> He said that larger studies into the vaccine would now follow. </div> <div> Story from BBC NEWS:</div> <div> http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/6940500.stm</div> <bR> <bR> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="442" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="438"><div> <B> <A NAME="estriol_for_ms_"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B><B>Estriol for MS?</B></div> </tD> </tR> </TABLE></div> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="442" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 1147 WIDTH="438"><div> LOS ANGELES, CA -- March 23, 2007 -- It has long been common knowledge that pregnant women with multiple sclerosis experience a sharp drop in the disease's symptoms during the course of their pregnancy. Some years back, Rhonda Voskuhl, MD, director of UCLA's Multiple Sclerosis Program, and her colleagues discovered the cause. They found that a female sex hormone called estriol, which is produced during pregnancy, was responsible for the suppression. Four years ago, Voskuhl followed that discovery with a pilot study in which 10 non-pregnant women with MS were given estriol, yielding what she described as "pretty remarkable" results — an 80% drop in inflammatory lesions in the brain, a hallmark of the disease. This month, Voskuhl begins a much larger trial of estriol, one that will involve 150 patients at multiple locations over the next two years. The prospects, she said, are exciting. Multiple sclerosis is an autoimmune disease of the central nervous system that attacks the tissue surrounding the brain's nerve fibers. This tissue, called myelin, can be thought of as the insulation wrapped around an electrical wire. When the myelin is damaged, the nerve's ability to send signals to and from the brain is interfered with, resulting in symptoms common to MS, including problems with balance, memory, vision loss and more. Currently, anti-inflammatory drugs used to treat MS lessen the symptoms and slow the progression of the disease. But they must be given by injection daily, weekly or monthly — depending on the drug — and are expensive, costing between $12,000 to $24,000 a year. Estriol is a hormone produced by the placenta that is virtually undetectable until pregnancy, when it progressively increases. It is thought that its role is to suppress a woman's immune system when she is pregnant, so that the fetus will not be seen by the body as a foreign "invader." "The beauty of estriol is that it can be given as a pill, not a shot, and also that it's not a new drug; it has decades of safety behind it," said Voskuhl, who holds the Jack H. Skirball Chair for Multiple Sclerosis in the UCLA Department of Neurology. For years, estriol has been in widespread use in Europe and Asia as hormone replacement therapy for women with menopausal symptoms. The fact that the pill already exists, she said, should dramatically reduce the cost of treatment. Most important of all, though, is that the drug potentially provides a one-two punch against MS, both reducing the ability of immune cells to attack the brain, as well as making the brain more resistant to damage if any immune cells do make it through. "It's a two-pronged approach an anti-inflammatory prong to reduce the attacks, but also a neuroprotective prong to make the brain suffer less damage in case of an attack," said Voskuhl. In all, seven institutions from around the nation will be involved in the two-year study. The investigators plan to recruit 150 women who have not previously been treated for MS. They will be given either estriol along with Copaxone, an MS drug currently in use, or a placebo along with Copaxone. "That way, no one will receive less than the standard of care," Voskuhl said. The team will measure relapse rates over the course of the trial. Initial funding of $667,000 for the trial is being provided by the Southern California Chapter of the National Multiple Sclerosis Society. The total cost of the trial is expected to be $4.7 million. For more information about the trial, please contact the UCLA MS program at (310) 825-7313. SOURCE: University of California, Los Angeles, Health Sciences </div> <bR> </tD> </tR> </TABLE></div> <bR> <bR> <bR> <div> <B> <A NAME="prolactin_may_ease_multiple_sclerosis"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B><B>Prolactin May Ease Multiple Sclerosis </B></div> <bR> <div> A hormone produced during pregnancy may benefit multiple sclerosis patients, a Canadian study finds.</div> <div> Multiple sclerosis (MS) affects about 2.5 million people worldwide. It occurs when the body's immune system attacks myelin, which insulates nerve cells and plays a critical role in the transmission of messages from cell to cell. Reductions in myelin lead to a progressive loss of sensation and movement in MS patients.</div> <div> Interestingly, MS goes into remission when women get pregnant. Since prolactin is a hormone that is produced during pregnancy, the researchers sought to determine if prolactin was the reason behind MS remission during pregnancy.</div> <div> "It was thought that during pregnancy, [women's] immune systems no longer destroyed the myelin," study author Samuel Weiss, of the Hotchkiss Brain Institute of the University of Calgary, said in a prepared statement. "But no previous study has tested whether pregnancy actually results in the production of new myelin, which may explain improvement of symptoms," he said. </div> <div> In the study, published in the Feb. 21 issue of the Journal of Neuroscience, researchers counted hundreds of cells in the brains and spinal cords of mice. They compared the cells in pregnant versus virgin female mice of the same age.</div> <div> The team found that the pregnant mice had twice as many myelin-producing cells and continued to generate new ones during pregnancy. Even after giving birth, the once-pregnant mice had 50 percent more myelin coating their nerve cells.</div> <div> The researchers also found that prolactin mimicked the effects of pregnancy, increasing both myelin production and repair in the mice. </div> <div> If future research confirms the benefits of prolactin in animal models of MS, Weiss says the hormone will be ready for testing as a treatment for people with MS.</div> <bR> <bR> <bR> <bR> <div>  <A NAME="vitamin_d_may_cut_multiple_sclerosis"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A>Vitamin D may cut multiple sclerosis risk,</div> <div>  </div> <div> People with higher levels of vitamin D have a markedly reduced risk of developing multiple sclerosis (MS), according to a study published on Tuesday that may point to a promising way to protect against the disease.</div> <div> MS is an incurable and often disabling disease of the central nervous system that appears most often among young adults and affects 2 million people globally.</div> <div> Researchers at the Harvard School of Public Health in Boston combed a massive repository of serum samples from more than 7 million U.S. military personnel to find 257 people who developed MS.</div> <div> Their samples were analyzed for vitamin D levels and compared with a group of randomly picked military personnel from the same broad population who did not develop MS.</div> <div> Among the white people studied, the chances of developing MS fell as vitamin D levels in the body rose, according to findings published in the Journal of the American Medical Association.</div> <div> Among whites, the majority of those in the study, the risks of MS fell 62 percent for those in the top fifth of vitamin D concentration.</div> <div> The researchers said this suggested that many cases of MS could be prevented if people raised their vitamin D intake.</div> <div> "This converges with a body of experimental evidence and other studies that strongly suggest that vitamin D could be truly protective," Alberto Ascherio, associate professor of nutrition and epidemiology at Harvard School of Public Health and the lead researcher, said in a telephone interview.</div> <div> The relationship between higher vitamin D levels and MS risk was absent in the black and Hispanic people in the study, researchers said, perhaps because so few were involved or both groups had overall lower levels of vitamin D than whites.</div> <div> Ascherio said more research was needed to nail down whether vitamin D leads to a reduced risk of MS.</div> <div> 'COULD BE ENORMOUS'</div> <div> "If it is true, the implication could be enormous for MS prevention," Ascherio said.</div> <div> Nicholas LaRocca of the National Multiple Sclerosis Society, an advocacy group that helped fund the study, called the findings promising but said it was premature to recommend that young people take vitamin D supplements to ward off MS.</div> <div> Vitamin D, a hormone manufactured naturally in the body, promotes the absorption of calcium necessary for developing and maintaining healthy teeth and bones.</div> <div> Calcium is also important to nerve cells, including the brain, while vitamin D also seems to act as a regulator of the immune system.</div> <div> The body makes the vitamin after being exposed to sunlight. Not many foods are naturally rich in vitamin D, but it is found in fatty fish such as salmon, and milk commonly is fortified with it.</div> <div> Vitamin D deficiency can lead to osteoporosis in adults or rickets in children.</div> <div> In MS, communication between the brain and other parts of the body is disrupted. Many experts believe MS is an autoimmune disease in which the body, through its protective system, attacks its own tissues. </div> <div> In some people, MS can lead to paralysis. </div> <div> Copyright © 2006 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. </div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="602" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 WIDTH="598"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="598" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <bR> <bR> <bR> <div> <B> <A NAME="soy_based_inhibitor_holds_promise_as_ms"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B><B>Soy-Based Inhibitor Holds Promise as MS Treatment </B></div> <div> Fri Dec 15, 2:01 PM ET </div> <div> FRIDAY, Dec. 15 (HealthDay News) -- A natural soy-based substance called Bowmann-Birk Inhibitor Concentrate (BBIC) improved the condition of animals with a disease similar to multiple sclerosis, a U.S. study says. </div> <div> One group of animals with the MS-like disease called autoimmune encephalomyelitis (EAE) received BBIC, while another group of animals with the same disease received an inert substance.</div> <div> "Animals that received BBIC were able to walk, while those that didn't get the drug were not," study leader Dr. A.M. Rostami, professor and chair of the department of neurology at Jefferson Medical College in Philadelphia, said in a prepared statement.</div> <div> The animals that received BBIC weren't cured of their illness and did walk with some limp or weakness. However, the results are promising, the researchers said.</div> <div> They also found that the central nervous systems of the animals that received BBIC had "significantly less inflammation and demyelination" than animals that didn't receive BBIC.</div> <div> "It's the first time that BBIC has been used in an EAE model and has shown significant disease suppression, and we hope it can eventually be used in humans," Rostami said.</div> <div> BBIC inhibits proteases, which are enzymes that play a major role in the inflammation and demyelination associated with multiple sclerosis, in which the myelin coating of nerve fibers become inflamed and scarred.</div> <div> The study was published Dec. 12 in the journal Multiple Sclerosis.</div> <div> More information</div> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="627" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER ROWSPAN=2 HEIGHT= 19 WIDTH="5"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="5" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="615"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="615" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER WIDTH="615"><div>  <A NAME="nicotine_and_ms"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A>NICOTINE AND MS</div> <bR> <div> Researchers working with mice report that it may be possible to protect people with multiple sclerosis from long-term nerve damage by boosting levels of a vitamin derivative in the nervous system. </div> <div> MS is a neurological disorder in which nerve fibers are damaged by inflammation thought to be triggered by the immune system's mistakenly attacking them. </div> <div> Damage to nerve fibers and to their fatty insulating tissues, disrupts nerves' ability to conduct electrical impulses to and from the brain. This produces the symptoms of MS that include fatigue, difficulty in walking, pain, spasticity and emotional and cognitive changes. </div> <div> Currently, MS treatments mainly protect against inflammation and loss of fatty insulating tissues, but don't completely prevent long-term scarring and breaking of the nerve fibers, for which there is no good treatment. And some of the drugs given to treat the early phases of the disease have severe side effects. </div> <div> Researchers at Children's Hospital Boston, the pediatric teaching hospital for Harvard Medical School, worked with mice that had an MS-like disease. </div> <div> The experiments, described Wednesday in the Journal of Neuroscience, showed that nicotinamide- a form of vitamin B3, or niacin - not only protected the animals' nerve fibers from degeneration and fatty insulating tissues loss, it also protected nerve fibers that have already lost insulation from degrading further. </div> <div> "We hope our work will initiate a clinical trial, and that nicotinamide could be used in real patients," said Dr. Shinjiro Kaneko, a research fellow at Children's who led the study. "In the early phase of MS, anti-inflammatory drugs may work, but long-term, you need to protect against axonal (nerve fiber) damage." </div> <div> On a scale of 1 to 5 (with 1 being only mild weakness in the tail; 4, paralysis in all four limbs, and 5, death from the disease), mice receiving the highest doses of daily nicotinamide injections under the skin had scores of 1 or 2, while mice not getting the vitamin had scores of 3 or 4. </div> <div> Nicotinamide significantly reduced neurological symptoms even when treatment was delayed for 10 days after the onset of disease in the mice, raising hopes that it can be effective in the later stages of MS in people. </div> <div> "The earlier therapy was started, the better the effect, but we hope nicotinamide can help patients who are already in the chronic stage," said Kaneko. </div> <div> Kaneko noted that since vitamin B3 is already used medically to treat high cholesterol and other disorders, it should have few side effects in humans being treated for MS. But he noted that the doses used in the mice would translate to much higher doses than typically given to people, so new tests for safety would be needed before there could be any tests to evaluate the drug's effectiveness. </div> </tD> </tR> </TABLE></div> <bR> <bR> <bR> <bR> <div> <B> <A NAME="natalizumab_for_relapsing_multiple"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B><B>Natalizumab for Relapsing Multiple Sclerosis</B></div> <div> <B>Chris H. Polman, M.D., Paul W. O'Connor, M.D., Eva Havrdova, M.D., Michael Hutchinson, M.D., Ludwig Kappos, M.D., David H. Miller, M.D., J. Theodore Phillips, M.D., Ph.D., Fred D. Lublin, M.D., Gavin Giovannoni, M.D., Andrzej Wajgt, M.D., Martin Toal, M.B., M.F.P.M., Frances Lynn, M.Sc., Michael A. Panzara, M.D., M.P.H., Alfred W. Sandrock, M.D., Ph.D., for the AFFIRM Investigators</B></div> <bR> <div> <B>     </B></div> <bR> <div> <B>ABSTRACT</B></div> <bR> <div> <B>Background Natalizumab is the first {alpha}4 integrin antagonist in a new class of selective adhesion-molecule inhibitors. We report the results of a two-year phase 3 trial of natalizumab in patients with relapsing multiple sclerosis.</B></div> <bR> <div> <B>Methods Of a total of 942 patients, 627 were randomly assigned to receive natalizumab (at a dose of 300 mg) and 315 to receive placebo by intravenous infusion every four weeks for more than two years. The primary end points were the rate of clinical relapse at one year and the rate of sustained progression of disability, as measured by the Expanded Disability Status Scale, at two years.</B></div> <bR> <div> <B>Results Natalizumab reduced the risk of sustained progression of disability by 42 percent over two years (hazard ratio, 0.58; 95 percent confidence interval, 0.43 to 0.77; P<0.001). The cumulative probability of progression (on the basis of Kaplan–Meier analysis) was 17 percent in the natalizumab group and 29 percent in the placebo group. Natalizumab reduced the rate of clinical relapse at one year by 68 percent (P<0.001) and led to an 83 percent reduction in the accumulation of new or enlarging hyperintense lesions, as detected by T2-weighted magnetic resonance imaging (MRI), over two years (mean numbers of lesions, 1.9 with natalizumab and 11.0 with placebo; P<0.001). There were 92 percent fewer lesions (as detected by gadolinium-enhanced MRI) in the natalizumab group than in the placebo group at both one and two years (P<0.001). The adverse events that were significantly more frequent in the natalizumab group than in the placebo group were fatigue (27 percent vs. 21 percent, P=0.048) and allergic reaction (9 percent vs. 4 percent, P=0.012). Hypersensitivity reactions of any kind occurred in 25 patients receiving natalizumab (4 percent), and serious hypersensitivity reactions occurred in 8 patients (1 percent).</B></div> <bR> <div> <B>Conclusions Natalizumab reduced the risk of the sustained progression of disability and the rate of clinical relapse in patients with relapsing multiple sclerosis. Adhesion-molecule inhibitors hold promise as an effective treatment for relapsing multiple sclerosis. (ClinicalTrials.gov number, NCT00027300 [ClinicalTrials.gov] .)</B></div> <bR> <div> <B> <A NAME="leptin_blocking"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B><B>LEPTIN BLOCKING</B></div> <bR> <div> <B>THURSDAY, Jan 12 (HealthDay News) -- Mice with an animal form of multiple sclerosis (MS) displayed slowed disease progression when scientists blocked the activity of a hormone called leptin, found primarily in fat cells.</B></div> <bR> <div> <B>The Italian team studied experimental autoimmune encephalomyelitis (EAE) in mice -- a commonly used animal model for researchers investigating MS.</B></div> <bR> <div> <B>"We are the first to report that leptin blockage can alter the EAE symptoms in mice," said Dr. Giuseppe Matarese, of the Universita di Napoli in Napoli, Italy. He is the lead author of the report, published in the February issue of the Journal of Clinical Investigation.</B></div> <bR> <div> <B>MS is an incurable inflammatory disease of the central nervous system marked by muscle weakness, numbness and loss of coordination. Disease severity can range from the relatively benign to cases involving serious disability and death. Many experts consider MS an autoimmune disease, in which the body attacks its own tissues, especially the protective myelin sheath surrounding nerves. About 400,000 people in the United States are diagnosed with MS, according to the National Multiple Sclerosis Society.</B></div> <bR> <div> <B>Leptin is known to play a role in regulating not only food intake and metabolism, but also the body's immune response. The hormone is expressed in active inflammatory lesions of the central nervous system during both MS and its mouse equivalent, EAE, Matarese said. Leptin also seems to increase the secretion of inflammatory mediators that help damage myelin.</B></div> <bR> <div> <B>However, using anti-leptin antibodies or disabled leptin receptors, Matarese's team effectively blocked leptin production in mice with EAE. The result: slowed EAE disease progression.</B></div> <bR> <div> <B>Blocking leptin reduced the number of disease relapses for the entire follow-up period of 120 days, the team found, suggesting the effect of leptin blockade is long lasting. The mice's "clinical score" -- reflecting symptoms -- was also reduced when leptin was blocked, as were levels of inflammation.</B></div> <bR> <div> <B>The new study builds on previous research, Matarese said. "In the past, we also showed that leptin administration to EAE-susceptible mice makes the EAE symptoms and brain inflammatory infiltration worse," he said.</B></div> <bR> <div> <B>Because leptin may play a role in other autoimmune disorders, the Italian researcher said his team will extend their work to include mouse models of type 1 diabetes and rheumatoid arthritis. They also plan to study the effects of leptin blockage in MS patients.</B></div> <bR> <div> <B>However, a spokesman for the National Multiple Sclerosis Society urged caution when interpreting the findings. Dr. John Richert, vice president for research and clinical programs for the society, said other groups have looked at controlling levels of leptin in blood and have not found differences between those with MS and those without, suggesting that leptin blockage may not become effective treatment.</B></div> <bR> <div> <B>Still, he said, the Italian research remains promising. "There is enough information there to indicate it warrants further study, but it's not a slam-dunk that it is going to be useful for people with MS."</B></div> <bR> <div> <B>More information</B></div> <bR> <div>    <A NAME="__vitamin_b12_demyelination"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><U>Vitamin B12, demyelination, remyelination and repair in multiple sclerosis.</U></div> <div>     Miller A, Korem M, Almog R, Galboiz Y.</div> <div>     Division of Neuroimmunology and Multiple Sclerosis Center, Carmel Medical Center, Haifa 34362, Israel. millera@tx.technion.ac.il</div> <bR> <div>     Multiple Sclerosis (MS) and vitamin B12 deficiency share common inflammatory and neurodegenerative pathophysiological characteristics. Due to similarities in the clinical presentations and MRI findings, the differential diagnosis between vitamin B12 deficiency and MS may be difficult. Additionally, low or decreased levels of vitamin B12 have been demonstrated in MS patients. Moreover, recent studies suggest that vitamin B12, in addition to its known role as a co-factor in myelin formation, has important immunomodulatory and neurotrophic effects. These observations raise the questions of possible causal relationship between the two disorders, and suggest further studies of the need to close monitoring of vitamin B12 levels as well as the potential requirement for supplementation of vitamin B12 alone or in combination with the immunotherapies for MS patients.</div> <div>     PMID: 15896807 [PubMed - indexed for MEDLINE]</div> <bR> <bR> <div> <B>     </B></div> <bR> <bR> <bR> <div> <B> <A NAME="tysabri_screening_news"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B><B>Tysabri Screening news</B></div> <bR> <div> By SHAWN POGATCHNIK, Associated Press WriterTue Aug 9, 6:24 PM ET</div> <bR> <div> About 2,000 patients who took the suspended MS-fighting drug Tysabri in clinical trials have been screened for a deadly disease, but none showed signs of contracting it, the Irish and U.S. companies jointly developing the drug said Tuesday.</div> <bR> <div> Elan Corp. PLC of Dublin and Biogen Idec Inc. of Cambridge, Mass., said they were taking "preliminary steps" to resume clinical trials of Tysabri, which was withdrawn from the U.S. market on Feb. 28 amid fears its use could cause progressive multifocal leukoencephalopathy, or PML, a rare brain disease.</div> <bR> <div> At the time, the companies said two multiple-sclerosis sufferers taking Tysabri had contracted PML, one fatally. They later confirmed a second fatal case of PML in a patient using Tysabri to treat Crohn's disease, a gastrointestinal disorder.</div> <bR> <div> On the Irish Stock Exchange, Elan shares surged nearly 40 percent to an intraday high of 8.52 euros ($10.50), then retreated to close at 7.40 euros ($9.14), still up 21 percent. Biogen shares rose $2.82, or 7.3 percent, to close at $41.24 Tuesday on the Nasdaq Stock Market.</div> <bR> <div> Analysts said the announcement signaled growing confidence by both companies that Tysabri would eventually receive renewed, if restricted, approval from the U.S. Food and Drug Administration.</div> <bR> <div> "The announcement is a clear signal to patients and the FDA of the companies' belief that Tysabri can make it back to the market," said Ian Hunter, an analyst for Goodbody Stockbrokers in Dublin.</div> <bR> <div> But other analysts cautioned that Tysabri's potential path back to the market faced obstacles on several fronts.</div> <bR> <div> The companies said they asked more than 2,000 MS sufferers who took Tysabri in clinical trials, mostly over a two-year period, to be screened for signs of PML. They said 91 percent have complied so far, of whom 99 percent had a neurological exam and 98 percent had an MRI scan.</div> <bR> <div> The screening produced "no new confirmed cases" of PML, the companies said.</div> <bR> <div> "Given the high unmet medical need in MS and the therapeutic benefit we have seen with Tysabri, we are encouraged by these safety findings," said Whaijen Soo, senior vice president of medical research at Biogen Idec.</div> <bR> <div> Both companies said they were still screening about 1,500 people who had taken Tysabri in clinical trials for testing its effectiveness against Crohn's disease and rheumatoid arthritis.</div> <bR> <div> Another unknown is whether PML will appear in any of approximately 5,000 people, chiefly in the United States, who began taking Tysabri during the drug's three-month availability on the U.S. market. The drug was administered every four weeks by intravenous infusion.</div> <bR> <div> The widower of the MS sufferer confirmed to have died of PML, 46-year-old Anita Smith of Colorado Springs, Colo., last month filed a wrongful death lawsuit against Elan and Biogen Idec seeking unspecified cash damages. According to the lawsuit, Anita Smith began taking Tysabri in April 2002 and died Feb. 24, 2005, four days before Tysabri's suspension from sale.</div> <bR> <div> "Patient safety remains our top priority," said Lars Ekman, executive vice president and president of research and development. "We are committed to finalizing the safety evaluation for Crohn's disease and rheumatoid arthritis, which is progressing well and on track to be completed by the end of the summer. We look forward to working with regulatory authorities to determine the path forward for Tysabri."</div> <bR> <div> Investors' growing optimism about Tysabri drove down shares of Serono SA, a Swiss company that makes an established MS drug, Rebif. In Zurich, Serono shares fell 1.3 percent to close at 844.5 Swiss francs ($670).</div> <bR> <div> ___</div> <bR> <div> On the Net:</div> <bR> <div> http://www.elan.com</div> <bR> <div> http://www.biogenidec.com</div> <bR> <div> <B><U> <A NAME="aspirin_for_fatigue_in_ms"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>PROVIGIL </U></B><B><U> FOR FATIGUE IN MS</U></B></div> <div> Fri Apr 22, 5:35 PM ET</div> <bR> <div> Provigil, a drug used to treat the sudden-sleep disorder narcolepsy, does not affect fatigue experienced by people with multiple sclerosis (MS), results of a trial suggest.</div> <bR> <div> However, a separate study found that aspirin may be of some benefit. Both studies appeared in the medical journal Neurology.</div> <bR> <div> Two small pilot studies recently showed a positive impact of Provigil, technically known as modafinil, on MS-related fatigue, note Dr. Bruno Stankoff, at Hopital de la Salpetriere in Paris and members of the French Modafinil Study Group, in the first study.</div> <bR> <div> To further investigate, the group randomly assigned 56 patients scoring 45 points or more on a fatigue scale to modafinil, and 59 to an inactive placebo.</div> <bR> <div> Both groups experienced decreased fatigue during the 35-day trial, but change in fatigue scores did not differ significantly between the two groups.</div> <bR> <div> In the second study, Dr. Dean M. Wingerchuk and colleagues point out that some MS patients using aspirin for other purposes report reduced fatigue.</div> <bR> <div> In crossover trial, 30 patients with MS-related fatigue took either aspirin twice daily or placebo for 6 weeks in random order, separated by a 2-week "washout" period.</div> <bR> <div> Average scores on one fatigue scale were lower during aspirin treatment (38.1 versus 42.5), but responses did not differ significantly on two other scales.</div> <bR> <div> Commenting in a related editorial, Drs. Steven R. Schwid of the University of Rochester, New York, and T. Jock Murray of Dalhousie University in Halifax, Nova Scotia, observe that "until we make progress in distinguishing fatigue from other MS symptoms, in identifying its mechanisms and in measuring it accurately, we will not make substantial progress in treating this disabling symptom."</div> <bR> <div> SOURCE: Neurology, April 12, 2005. </div> <div>  <A NAME="therapy_slows_down_multiple_sclerosis"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><B>Therapy Slows Down Multiple Sclerosis </B>   Oct 13, 2004</div> <div> WEDNESDAY, Oct. 13 (HealthDayNews) -- A therapy designed to boost the body's immune system could reduce the risk of a second attack of symptoms related to multiple sclerosis, according to an article in the October issue of The Archives of Neurology.</div> <bR> <div> Multiple sclerosis is a chronic inflammatory disease in which the body's myelin -- the material that covers and insulates nerve cells in the brain and spinal cord -- begins to deteriorate. This causes impairment of motor, sensory, visual and cognitive funcion.</div> <bR> <div> Israeli researchers found that intravenous immunoglobulin therapy applied after the first signs of MS significantly reduced the probability of developing clinically definite multiple sclerosis.</div> <bR> <div> Patients receiving the therapy also suffered fewer brain lesions.</div> <bR> <div> The research was conducted by doctors at the Sheba Medical Center in Tel-Hoshomer.</div> <bR> <div> <B><U> <A NAME="multiple_sclerosis"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>Multiple Sclerosis</U></B></div> <div> From WebMD Health        with       The Cleveland Clinic</div> <bR> <div> Q  What is multiple sclerosis?</div> <div> A  MS is an autoimmune disease, whereby the body's own immune system, which normally targets and destroys substances foreign to the body such as bacteria, mistakenly attacks normal tissues. In MS, the immune system attacks the brain and spinal cord, two components of the central nervous system.</div> <bR> <div> Q  What causes MS?</div> <div> A    Doctors still don't understand what causes MS, but there are interesting data that suggest that genetics, a person's environment, and possibly even a virus may play a role.</div> <bR> <div> Researchers believe that MS may be inherited (passed on from parents to children). First, second and third degree relatives of people with MS are at increased risk of developing the disease. Siblings of an affected person have a 2%-5% risk of developing MS.</div> <bR> <div> Some scientists theorize that MS develops because a person is born with a genetic predisposition to react to some environmental agent, which, upon exposure, triggers an autoimmune response.</div> <bR> <div> In addition, some studies have suggested that many viruses such as measles, herpes, and the flu viruses may be associated with MS. To date, however, this belief has not been proven.</div> <bR> <div> Q  What are the symptoms of MS?</div> <div> A   The onset of MS may be dramatic or so mild that a person doesn't even notice any symptoms.</div> <bR> <div> The most common early symptoms of MS include:</div> <bR> <div>     * Tingling</div> <div>     * Numbness</div> <div>     * Loss of balance</div> <div>     * Weakness in one or more limbs</div> <div>     * Blurred or double vision</div> <bR> <div> Less common symptoms may include:</div> <bR> <div>     * Slurred speech</div> <div>     * Sudden onset of paralysis</div> <div>     * Lack of coordination</div> <bR> <div> As the disease progresses, other symptoms may include heat sensitivity, fatigue, changes in thinking or perception, and sexual disturbances.</div> <bR> <div> Q   Is multiple sclerosis fatal, contagious, or hereditary?</div> <div> A MS is not considered a fatal, contagious or directly inherited disease, although there may be a familial predisposition of MS. Prevalence in families of individuals with MS is somewhat higher than in the general population.</div> <bR> <div> Q Is there a cure for MS?</div> <div> A  Unfortunately, there is not a cure for multiple sclerosis, but there are many drugs that may slow down the progression of the disease. There are also many treatments available that can help a person with MS manage their symptoms and live a productive and fulfilling life.</div> <bR> <div> Q  Am I going to end up in a wheelchair?</div> <div> A  Most people with MS usually get around without assistance; however, there may be a time when you will need some type of assistance. Approximately 25% of people with MS will need a wheelchair. There may be a time when you would need to use some type of other walking aide like a cane or walker.</div> <bR> <div> Q  How do I decide which therapy is best for me?</div> <div> A    Choosing to begin therapy can be a difficult decision to make; learning about your treatment options and discussing them with your doctor is the first step in deciding what treatment to begin. Some other factors to consider are effectiveness, side effects, your current lifestyle, and how the therapy is given.</div> <bR> <div> Q    How do people with MS benefit from deep brain stimulation?</div> <div> A   The main purpose of deep brain stimulation is to control the arm tremor. While tremor of the head and body may be helped, the decision to have surgery should be based on the goal of decreasing arm tremor. In the case of multiple sclerosis, other problems such as loss of vision, sensation, or strength are not helped by deep brain stimulation.</div> <div> Q  What alternative therapies are recommended for MS?</div> <div> A       * Positive Attitude. Having a positive outlook cannot cure MS, but it can lower your stress and help you feel better.</div> <div>     * Exercise. Exercises, such as tai chi and yoga can lower your stress, increase relaxation, and increase your energy, balance, and flexibility. As with any exercise program, check with your doctor before getting started.</div> <div>     * Diet. It is important for people with MS to follow a healthy, well-balanced diet. Ask your doctor what diet is right for you.</div> <bR> <div> Q       What is optic neuritis?</div> <div> A   Optic neuritis is the inflammation of the optic nerve, the nerve located in the back of the eye that transmits light and visual images to the brain and is responsible for vision. According to the National Multiple Sclerosis Society, 55% of people with MS will have an episode of optic neuritis. Frequently, it's the first symptom of the disease. Although having optic neuritis is very suggestive of MS, it does not mean that a person has or will get MS.</div> <bR> <div> The symptoms of optic neuritis are the acute onset of any of the following:</div> <bR> <div>     * Blurred vision</div> <div>     * Graying of vision</div> <div>     * Blindness in one eye</div> <bR> <div> It's rare that both eyes are affected simultaneously. And pain is rare. Loss of vision tends to worsen over the course of a few days before getting better. This usually takes about 4-12 weeks. Treatment may include intravenous and/or oral steroids to control the inflammation.</div> <bR> <div> Reviewed by the doctors at the Mellen Center for Multiple Sclerosis at The Cleveland Clinic.</div> <bR> <div> Edited by Charlotte E. Grayson, MD, Nov. 2002, WebMD.</div> <bR> <div> Copyright © 2003, The Cleveland Clinic.</div> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <div>  <A NAME="advances_in_multiple_sclerosis_research_"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A>Advances in Multiple Sclerosis Research and Treatment: An Expert Interview With Barry Singer, MD</div> <bR> <div> Medscape Neurology & Neurosurgery 6(1), 2004. © 2004 Medscape</div> <bR> <div> Editor's Note:</div> <div> Multiple sclerosis (MS) is the most common cause of neurologic disability in young adults, and it exhibits significant clinical, radiologic, and pathologic heterogeneity. MS remains a complex disease to manage, and no curative therapy exists. Furthermore, much debate remains about what few, available treatments should be enlisted, as well as when and for how long. Some issues, such as neutralizing antibodies to interferon-beta, one of the mainstays of MS treatment, have emerged as a clinical controversy in the field. Scott Williams, Senior Editor, Medscape Neurology & Neurosurgery, interviewed Barry Singer, MD, Assistant Professor of Clinical Neurology at Washington University School of Medicine in St. Louis, Missouri, to discuss these and other important issues in the management of patients with MS, including new research presented at the 56th Annual Meeting of the American Academy of Neurology.</div> <bR> <div> Medscape: For patients with newly diagnosed relapsing-remitting multiple sclerosis (MS), how do you choose the most appropriate treatment?</div> <bR> <div> Dr. Singer: I determine the goals for therapy with each individual patient. Efficacy, in terms of reducing relapses, MRI lesions, and most importantly progression of disability, drives my decision-making process. Route of administration, dosing frequency, tolerability, and potential risks are secondary.</div> <bR> <div> Medscape: What are the most pressing controversies or unresolved questions currently facing clinicians who treat patients with MS?</div> <bR> <div> Dr. Singer: The most challenging problem I face with my patients is how to treat progressive disease. Interferons have been successful for patients with secondary progressive disease, but only when the patients are actively relapsing. Novantrone (mitoxantrone) is another option for secondary progressive disease. Of course, treatment for primary progressive disease is desperately needed. Data presented at this year's AAN Meeting showed no significant benefit from either Copaxone (glatiramer acetate) or Novantrone for patients with primary progressive MS. The focus for treatment development of progressive patients will likely have to shift from anti-inflammatory to neuroprotective therapies.</div> <bR> <div> Medscape: The clinical significance of neutralizing antibodies to interferons in the context of MS treatment is obviously a controversial topic. How would you characterize the differing views of investigators in this area of research, and what implications does that have for the clinician specializing in MS?</div> <bR> <div> Dr. Singer: The spectrum of views regarding neutralizing antibodies is extreme. Some MS specialists never check for antibodies and deem them irrelevant. Others insist that the development of neutralizing antibodies to interferon makes the agent as good as placebo. On the basis of data from the Prevention of Relapses and Disability by Interferon-beta-1a Subcutaneously in Multiple Sclerosis (PRISMS) trial, the relapse rate over 4 years was not statistically different, whether patients were neutralizing-antibody-positive or -negative. The relapse rate was higher over the course of years 3-4 in the presence of neutralizing antibodies, but the difference disappeared at the end of year 4. At 64 weeks in the EVIDENCE trial, neutralizing-antibody-positive patients receiving subcutaneous Rebif (interferon-beta-1a) had more relapses and MRI activity than the neutralizing-antibody-negative patients receiving the same drug, but had fewer relapses and MRI activity than patients receiving Avonex (intramuscular interferon-beta-1a formulation). My initial selection of interferon is primarily based on overall efficacy rather than the risk of developing neutralizing antibodies. If a patient is doing poorly on interferon, I will check neutralizing antibody status to help determine the next treatment options.</div> <bR> <div> Medscape: In your opinion, what were the most compelling data on neutralizing antibodies at AAN?</div> <bR> <div> Dr. Singer: Only limited data were presented about neutralizing antibodies. Dr. Susan Goelz of Biogen Idec presented a poster of a study of 49 patients who were switched to Avonex after developing neutralizing antibody titers >/= 5 while on Betaseron (interferon-beta-1b). Of the 39 patients with initial titers of 5-99, 90% were neutralizing-antibody-negative at the end of 6 years. Of the 10 patients with titers >/= 100, 5 patients became neutralizing-antibody-negative at the end of 6 years. The median time to become neutralizing-antibody-negative was 6 months.</div> <bR> <div> An open-label study from Torino, Italy, looked at the incidence of neutralizing antibodies and its effect on relapse rate and disability in 78 patients. The trial enrolled only 13 neutralizing-antibody-positive patients in total on Avonex, Betaseron, or Rebif 22 mcg 3 times weekly. Patients who were neutralizing-antibody-negative had a greater reduction in relapses as compared with neutralizing-antibody-positive patients. A higher percentage of neutralizing-antibody-positive patients vs neutralizing-antibody-negative had worsening of the Expanded Disability Status Scale (EDSS) of >/= 1 point over the course of 3 years.</div> <bR> <div> Medscape: Although there is evidence that disease-modifying therapies reduce the relapse rate and are beneficial in the short term, what types of studies will need to be done to determine whether long-term disability related to MS is being reduced?</div> <bR> <div> Dr. Singer: The pivotal trial using Avonex did demonstrate a 36% reduction in the progression of disability over 2 years as compared with placebo, but long-term data are lacking. The PRISMS 7-8 year follow-up data demonstrated the least disability progression in the group of patients randomized to the high-dose (44 mcg 3 times weekly) Rebif from the treatment onset. Although years 4-8 were open-label with retrospective data collection, the results are fairly compelling because 68% of all the patients receiving this formulation and 74% of the high-dose patients were included in the final analysis. The 3-year trial of Betaseron for relapsing-remitting MS did not show a significant reduction in disability, but the European trial of this agent for patients with secondary progressive disease did show significant benefit. Eight-year data on disability are being collected from the European study.</div> <bR> <div> Copaxone did not provide a significant impact on confirmed disability in the pivotal 2-year clinical trial. Open-label results at 10 years showed lower disability in patients still receiving Copaxone monotherapy, but most patients were no longer on this regimen. A long-term trial of relapsing-remitting patients randomized blindly to placebo vs active drug to prove reduction of disability over a period of years is unlikely to occur at this point, primarily because placing patients on placebo for a period of years would be considered unethical.</div> <bR> <div> Medscape: At AAN, there were long-term follow-up reports of patients treated with disease-modifying therapies. What did the longer-term data show in that regard?</div> <bR> <div> Dr. Singer: The long-term PRISMS follow-up (7-8 years) showed strong beneficial effects of using high-dose Rebif (44 mcg 3 times weekly) from the onset. The increase in the burden of disease seen on T2 MRI for these patients was only 5.0%. Those patients initially placed on 22 mcg 3 times weekly or placebo demonstrated a 17.4% and 24.5% increase, respectively, on burden of disease. The 5-year CHAMPIONS Study showed a 47% reduction in relapse rate for patients who were begun on Avonex immediately after a monophasic demyelinating event. Only 36% of patients treated immediately developed clinically definite MS at 5 years in contrast to 49% in the delayed-treatment group. The 10-year open-label Copaxone trial demonstrated less disability in 108 patients receiving ongoing Copaxone monotherapy than the 47 patients who withdrew from the study and were reached for long-term follow-up. An additional 77 patients withdrew, but long-term follow-up was not available. More disability in the withdrawal group may reflect treatment failure since 29% of patients withdrew to switch or combine therapies and 26% withdrew because the patient was perceived as clinically worsening. From the original EUSPMS trial of 718 patients, 222 entered a long-term follow-up study ongoing to 8 years. Preliminary data indicate less disability in the cohort of patients who initially received Betaseron instead of placebo.</div> <bR> <div> Medscape: What are your insights about data at AAN concerning experimental immunomodulatory therapies, such as daclizumab and laquinimod, and the potential therapeutic benefit of supplements, such as alpha-lipoic acid?</div> <bR> <div> Zenapax (daclizumab) is a monoclonal antibody specific for the interleukin-2 receptor that inhibits lymphocyte activation. In an open-label trial of 20 patients, 10 patients had a reduction in disability, 9 patients had stable disability, and 1 dropped out because of paresthesias. The percentage of active MRI scans decreased significantly from 39% to 13% with treatment. This monthly infusion therapy seems very promising, but double-blind trials will be needed.</div> <bR> <div> Laquinimod, an oral immunomodulatory agent, demonstrated a 44% reduction in the mean number of cumulative active MRI lesions. However, the result only had marginal statistical significance (P = .0498) despite triple-dose gadolinium administration. As a previous Linomide (roquinimex) clinical trial investigator, I have concerns about the similarities of laquinimod to Linomide because cases of myocardial infarctions occurred in MS patients on Linomide.</div> <bR> <div> Finally, the antioxidant alpha-lipoic acid was given orally to 29 patients for 14 days. Levels of serum matrix metalloproteinase-9 were reduced, which might inhibit migration of activated autoreactive T cells in the brain. The results are interesting, but more clinical parameters, such as MRI, will need to be studied to assess therapeutic benefit.</div> <bR> <div> Suggested Readings</div> <bR> <div> Barkhof F, Polman CH, Sandberg-Wollheim M, et al. Oral treatment with laquinimod reduces development of active MRI lesions in relapsing MS. Program and abstracts from the 56th Annual Meeting of the American Academy of Neurology; April 24-May 1, 2004; San Francisco, California. Abstract 12.005.</div> <bR> <div> Goelz SE. The persistence of neutralizing antibodies to interferon beta (IFNbeta) over 6 years of treatment in MS patients is dependent on titer and IFNbeta product. Program and abstracts from the 56th Annual Meeting of the American Academy of Neurology; April 24-May 1, 2004; San Francisco, California. Abstract P02.124.</div> <bR> <div> Johnson KP, Panitch HS, Ford CC, Lisak RP; the Copaxone Study Group. Longterm slowing of disability progression in patients receiving continuous glatiramer acetate compared with those withdrawing from therapy: 10 year results from an ongoing trial. Program and abstracts from the 56th Annual Meeting of the American Academy of Neurology; April 24-May 1, 2004; San Francisco, California. Abstract S20.004.</div> <bR> <div> Kinkel RP, Kollman C, Glassman A, et al. Interferon beta 1a (Avonex) delays the onset of clinically definite MS over 5 years of treatment: results from CHAMPIONS study. Program and abstracts from the 56th Annual Meeting of the American Academy of Neurology; April 24-May 1, 2004; San Francisco, California. Abstract S29.006.</div> <bR> <div> Li D, Abdalla JA. Long-term observational follow-up of the PRISMS cohort: analyses of MRI BOD shows benefit of high dose, high-frequency IFN beta-1a (Rebif copyright). Program and abstracts from the 56th Annual Meeting of the American Academy of Neurology; April 24-May 1, 2004; San Francisco, California. Abstract P02.118.</div> <bR> <div> Malucchi S, Sala A, Gilli F, Bottero R, et al. Neutralizing antibodies reduce the clinical efficacy of interferon beta products in patients with multiple sclerosis. Program and abstracts from the 56th Annual Meeting of the American Academy of Neurology; April 24-May 1, 2004; San Francisco, California. Abstract P02.125.</div> <bR> <div> Panitch H, Goodin DS, Francis G, et al. Randomized comparative study of interferon beta-1a treatment regimens in MS: the EVIDENCE trial. Neurology. 2002;59:1496-1506.</div> <bR> <div> Polman C, Kappos L, White R, et al; European Study Group in Interferon Beta-1b in Secondary Progressive MS. Neutralizing antibodies during treatment of secondary progressive MS with interferon beta-1b. Neurology. 2003;60:37-43.</div> <bR> <div> PRISMS Study Group. Randomised, double-blind, placebo-controlled study of interferon beta-1a in relapsing-remitting multiple sclerosis. Lancet. 1998;352:1498-1504.</div> <bR> <div> PRISMS Study Group and University of British Columbia MS/MRI Analysis Group. PRISMS-4: long-term efficacy of interferon-beta-1a in relapsing MS. Neurology. 2001;56:1628-1636.</div> <bR> <div> Rose JW, Watt HE, White A, Martin R. Treatment of multiple sclerosis with daclizumab. Program and abstracts from the 56th Annual Meeting of the American Academy of Neurology; April 24-May 1, 2004; San Francisco, California. Abstract S12.002.</div> <bR> <div> Yadav V, Lovera J, Marracci G, et al. Randomized, double-blind, placebo controlled pilot trial of alpha lipoic acid in multiple sclerosis: pharmacokinetics, safety and effects on matrix metalloproteinase-9. Program and abstracts from the 56th Annual Meeting of the American Academy of Neurology; April 24-May 1, 2004; San Francisco, California. Abstract S29.003.</div> <bR> <bR> <div> Disclosure: Barry A. Singer, MD, has disclosed that he has received grants for clinical research from Pfizer/Serono as well as served as an advisor or consultant for Pfizer/Serono, Biogen, and Teva Neuroscience. Dr. Singer has reported that he does not discuss any investigational or unlabeled uses of commercial products in this activity.</div> <bR> <div> Disclosure: Scott Williams has no significant financial interests or relationships to disclose.</div> <bR> <div> <B><U> <A NAME="discovery_science_meets_multiple"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>Discovery Science Meets Multiple Sclerosis</U></B></div> <div> Jerry Wolinsky, MD</div> <div> University of Texas Health Science Center at Houston</div> <bR> <div> A new and potentially quite powerful approach is beginning to be applied throughout medicine. It involves discovery science, which is possibly just a euphemism for a grand fishing exhibition but likely is much more profound. The most informative use of discovery science incorporates spinoffs of the human genome project and advances in microarray and high-throughput technology. It uses these tools to define novel biomarkers for a variety of clinical purposes: diagnosis and subcategorization of disease, identification of therapeutic response potential, and early prediction of therapeutic outcome. In some instances, this science holds the possibility for illuminating new concepts of disease etiology and pathogenesis.</div> <bR> <div> Discovery science consists mainly of expression genomics—determining the relative levels of messenger RNA expressed in diseased tissues as compared with normal tissues; in tissues such as mononuclear cells in the blood of diseased patients as compared with normal persons; or in patients embarking on therapy. Genomics can be enriched by searching for novel serum proteins (proteomics).</div> <bR> <div> Applications of discovery science may be part of either a restricted or an unbiased search. The restricted, or highly directed, forms of this type of research require considerable insight into the mechanisms of a particular disease, so that the search can focus on selected genes, signals, and molecules. With the unbiased form of this research, investigators require the largest possible panel of molecules that can be studied. Unbiased searching has broad application in medicine, but a single example of its upcoming use in a large clinical trial of multiple sclerosis (MS) can serve as an illustration.</div> <bR> <div> MS is viewed as a complex disease with strong genetic and environmental influences and a dominant immunologic component. A number of genes are implicated in conferring risk, only one of which is reasonably well established: the HLA-DR2 (DRB1*1501, DQB1*0602) haplotype. Other genetic influences are less well established, but some, such as the gene APOE e4, may confer susceptibility to more severe clinical disease. At the immunologic level, a new predictive tool has emerged for use at the time of clinical onset: the presence of immunoglobulins against myelin antigens from the central nervous system has been recently associated with the likelihood of near-term disease activity. This approach complements the use of magnetic resonance imaging to predict disease burden.</div> <bR> <div> Increasingly, investigators have focused on transcriptional profiling of peripheral blood mononuclear cells to identify possible biomarkers that may distinguish persons with MS from those without the disease. This research has been conducted using complementary DNA microarray targets of about 12,000 genes. Similarly, proteomic studies have identified molecules (as yet incompletely defined) that may differentiate patients with MS from those without the disease.</div> <bR> <div> Despite uncertainty over the cause of MS, the course of the disease can be modified by several classes of immunomodulatory drugs. Researchers increasingly suspect that the limited benefits of currently approved immunomodulatory drugs may in part reflect the heterogeneity of the disease, if not the genetic background of individual patients.</div> <bR> <div> Against this background stands a new trial that will compare two classes of immunomodulating drugs (interferon beta-1a and glatiramer acetate) as monotherapy or combined therapy for previously untreated relapsing MS. This is an investigator-initiated clinical trial, initiated and directed by Fred Lublin at Mt. Sinai School of Medicine and funded by the National Institute of Neurological Disorders and Stroke. As an adjunct to its clinical arm, the trial will also investigate the utility of the unbiased form of discovery science. Roland Martin at the Neuroimmunology Branch will head this collaboration, which includes Gary Cutter at the University of Alabama at Birmingham and myself as co–principal investigators. We hope to study most of the clinical cohort of 1,000 subjects for single-nucleotide polymorphisms. We will use expression profiling to interrogate nearly the entire set of human genes; mass spectrometry–based proteomics with subsequent identification of informative proteins; and human leukocyte antigen typing at entry into the trial, with repeated expression profiling and proteomics at 6 and 12 months into therapy and at the trial's conclusion at 3 years.</div> <bR> <div> It is realistic to expect that these studies will define complex profiles that suggest which patients have the potential to respond to immunomodulatory drugs, which of these responders will show the effects of therapy early, and which patients will have a good clinical outcome at 3 years. Perhaps more fanciful is the hope for unanticipated findings that could provide a more fundamental understanding of the disease and point to novel pharmaceutical interventions.</div> <bR> <div> The success of discovery science when applied to arguably simple diseases, such as leukemia and solid tumors, is well established. Whether this approach can be successfully used in a complex disease such as MS remains to be seen.</div> <bR> <div> jerrywolinskymd@webmd.net</div> <bR> <div>  <A NAME="calabresi_article"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="765" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#004A8A HEIGHT= 13799 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="760" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 13770 ><NOBR><bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="757" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 13725 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="757" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=4 BGCOLOR=#FFFFFF HEIGHT= 16 WIDTH="747"><div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFFF HEIGHT= 13677 WIDTH="12"><div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFFF WIDTH="685"><div> <A HREF="http://www.aafp.org/afp/20041115/contents.html" TARGET="_top" TITLE="http://www.aafp.org/afp/20041115/content"><U><IMG SRC="353f4490.png" border=0 width="500" height="73" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></U></A></div> <bR> <div> <B>Diagnosis and Management of Multiple Sclerosis</B></div> <div> PETER A. CALABRESI, M.D., <I>Johns Hopkins University School of Medicine, Baltimore, Maryland</I></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="688" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 497 WIDTH="519"><div> Multiple sclerosis, an idiopathic inflammatory disease of the central nervous system, is characterized pathologically by demyelination and subsequent axonal degeneration. The disease commonly presents in young adults and affects twice as many women as men. Common presenting symptoms include numbness, weakness, visual impairment, loss of balance, dizziness, urinary bladder urgency, fatigue, and depression. The diagnosis of multiple sclerosis should be made by a physician with experience in identifying the disease. Diagnosis should be based on objective evidence of two or more neurologic signs that are localized to the brain or spinal cord and are disseminated in time and space (i.e., occur in different parts of the central nervous system at least three months apart). Magnetic resonance imaging with gadolinium contrast, especially during or following a first attack, can be helpful in providing evidence of lesions in other parts of the brain and spinal cord. A second magnetic resonance scan may be useful at least three months after the initial attack to identify new lesions and provide evidence of dissemination over time. It is critical to exclude other diseases that can mimic multiple sclerosis, including vascular disease, spinal cord compression, vitamin B<FONT SIZE="1" COLOR="#660099" FACE="Arial" >12</FONT> deficiency, central nervous system infection (e.g., Lyme disease, syphilis), and other inflammatory conditions (e.g., sarcoidosis, systemic lupus erythematosus, Sjögren's syndrome). Symptom-specific drugs can relieve spasticity, bladder dysfunction, depression, and fatigue. Five disease-modifying treatments for multiple sclerosis have been approved by the U.S. Food and Drug Administration. These treatments are partially effective in reducing exacerbations and may slow progression of disability. (Am Fam Physician 2004;70:1935-44. Copyright© 2004 American Academy of Family Physicians.)</div> </tD> <tD VALIGN=CENTER WIDTH="10"><div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> <tD VALIGN=TOP><NOBR><div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="156" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 245 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="136" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 124 ><NOBR><div> <IMG SRC="35514110.png" border=0 width="20" height="17" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </NOBR></tD> <tD VALIGN=TOP WIDTH="105"><div> A PDF version of this document is available. <FONT SIZE="2" COLOR="#004A8A" FACE="Arial" ><A HREF="http://www.aafp.org/afp/20041115/1935.pdf" TARGET="_top" TITLE="http://www.aafp.org/afp/20041115/1935.pd"><U><U>Download PDF now </U></U></A></FONT>(10 pages /273 KB).</div> </tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 89 WIDTH="24"><div>  </div> </tD> <tD VALIGN=TOP WIDTH="105"><div> <A HREF="http://www.aafp.org/afpsort.xml" TARGET="_top" TITLE="http://www.aafp.org/afpsort.xml"><U><U>See page 1845 for definitions of strength-of-recommendation labels. </U></U></A></div> </tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="119" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="LEFT" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 210 WIDTH="115"><div> Proposed diagnostic criteria for multiple sclerosis include magnetic resonance imaging findings, as well as clinical features.</div> </tD> </tR> </TABLE></div> <div> <B>M</B><FONT SIZE="2" COLOR="#660099" FACE="Arial" >ultiple sclerosis (MS) typically presents in adults who are 20 to 45 years of age. Occasionally, the disease presents in childhood or late middle age. Twice as many women are affected as men, and persons of Northern European descent appear to be at highest risk for the disease.</FONT></div> <div> The onset of MS may be insidious or sudden. Common presenting symptoms include monocular visual impairment with pain (optic neuritis), paresthesias, weakness, and impaired coordination <I>(Table 1). </I>Frequent accompanying signs and symptoms include bladder urgency or retention, constipation, sexual dysfunction, fatigue, depression, diplopia, gait and limb ataxia, and Lhermitte's sign (electrical sensation down the spine on neck flexion).</div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="402" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 15 WIDTH="398"><div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 649 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 18 WIDTH="387"><div> TABLE 1</div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 ><NOBR><div> <B>Common Symptoms and Signs of Multiple Sclerosis</B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="387"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="387" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 551 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 20 WIDTH="384"><div> <B>Symptoms</B></div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 WIDTH="384"><div> Depression</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 WIDTH="384"><div> Dizziness or vertigo</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 WIDTH="384"><div> Fatigue</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 WIDTH="384"><div> Heat sensitivity</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 38 WIDTH="384"><div> Lhermitte's sign (electrical sensation down the spine on neck flexion)</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 WIDTH="384"><div> Numbness, tingling, pain</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 WIDTH="384"><div> Urinary bladder dysfunction</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 ><NOBR><div> Visual impairment (monocular or diplopia)</div> </NOBR></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 WIDTH="384"><div> Weakness</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 20 WIDTH="384"><div> <B>Signs</B></div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 WIDTH="384"><div> Action tremor</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 ><NOBR><div> Decreased perception of pain, vibration, or position</div> </NOBR></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 WIDTH="384"><div> Decreased strength</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 ><NOBR><div> Hyperreflexia, spasticity, Babinski's sign</div> </NOBR></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 WIDTH="384"><div> Impaired coordination and balance</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 57 WIDTH="384"><div> Impaired visual acuity or red color perception with optic disc pallor and afferent pupillary defect; disconjugate eye movements</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 18 WIDTH="384"><div> Nystagmus</div> </tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 15 WIDTH="398"><div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> </tR> </TABLE></div> <div> MS frequently is overlooked because initial symptoms resolve spontaneously in most patients. Relapses occur within months or years. In some patients, however, MS has a primary progressive course from onset.</div> <div> Diagnosis</div> <div> The diagnosis of MS is based on the presence of central nervous system (CNS) lesions that are disseminated in time and space (i.e., occur in different parts of the CNS at least three months apart), with no better explanation for the disease process. Because no single test is totally reliable in identifying MS, and a variety of conditions can mimic the disease <I>(Table 2), </I>diagnosis depends on clinical features supplemented by the findings of certain studies.</div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="402" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 15 WIDTH="398"><div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 466 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 18 WIDTH="387"><div> TABLE 2</div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 ><NOBR><div> <B>Conditions That Can Mimic Multiple Sclerosis</B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="387"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="387" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 311 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 57 WIDTH="384"><div> CNS infection (e.g., Lyme disease, syphilis, human immunodeficiency virus infection, human T-lymphotrophic virus type I)</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 38 WIDTH="384"><div> CNS inflammatory condition (e.g., sarcoidosis, systemic lupus erythematosus, Sjögren's syndrome)</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 38 WIDTH="384"><div> CNS microvascular disease (e.g., disease caused by hypertension, diabetes mellitus, vasculitis, CADASIL)</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 38 WIDTH="384"><div> Genetic disorder (e.g., leukodystrophy, hereditary myelopathy, mitochondrial disease)</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 57 WIDTH="384"><div> Structural or compressive condition of the brain and spinal cord (e.g., cervical spondylosis, tumor, herniated disc, Chiari's malformation)</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 18 WIDTH="384"><div> Vitamin B<FONT SIZE="1" COLOR="#660099" FACE="Arial" >12</FONT> deficiency</div> </tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="387"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="387" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 28 WIDTH="387"><div> CNS = central nervous system; CADASIL = cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.</div> </tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 15 WIDTH="398"><div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> </tR> </TABLE></div> <div> Magnetic resonance imaging (MRI) has been shown to be highly sensitive in detecting clinically silent MS plaques. Consequently, findings of this imaging modality are included in diagnostic criteria that have been proposed by one set of investigators.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >1</FONT> The major advantage of the proposed criteria is that an early diagnosis of MS can be made if an MRI scan performed three months after a clinically isolated attack demonstrates formation of a new lesion. The proposed diagnostic criteria also define MRI lesion characteristics that increase the likelihood of MS, including number of lesions (nine or more), location of lesions (position abutting the ventricles; juxtacortical, infratentorial, or spinal position), and lesion enhancement with the use of contrast medium <I>(Table 3).</I></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="402" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 15 WIDTH="398"><div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 585 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 18 WIDTH="387"><div> TABLE 3</div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 36 WIDTH="387"><div> <B>MRI Lesion Characteristics Suggestive of Multiple Sclerosis</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="387"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="387" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 413 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 20 WIDTH="384"><div> <B>Brain lesions</B></div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 38 WIDTH="384"><div> High signal on T<FONT SIZE="1" COLOR="#660099" FACE="Arial" >2</FONT>-weighted and FLAIR MRI sequences (more than nine lesions)</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 38 WIDTH="384"><div> When actively inflamed, often enhanced with gadolinium contrast</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 ><NOBR><div> Position abutting ventricles (often perpendicular)</div> </NOBR></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 ><NOBR><div> Juxtacortical position (gray-white junction)</div> </NOBR></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 38 WIDTH="384"><div> Involvement of brainstem, cerebellum, or corpus callosum</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 20 WIDTH="384"><div> <B>Spinal cord lesions</B></div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 ><NOBR><div> One or two vertebral segments in length</div> </NOBR></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 38 WIDTH="384"><div> Incomplete cross-sectional involvement (dorsolateral common)</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 ><NOBR><div> Less likely to enhance with gadolinium contrast</div> </NOBR></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 19 WIDTH="384"><div> No cord swelling</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 18 WIDTH="384"><div> Better seen with STIR MRI sequences</div> </tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="387"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="387" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 28 WIDTH="387"><div> MRI = magnetic resonance imaging; FLAIR = fluid attenuation inversion recovery; STIR = short tau inversion recovery.</div> </tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 15 WIDTH="398"><div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> </tR> </TABLE></div> <div> confirmatory studies</div> <div> <I>CNS Imaging. </I>A brain MRI scan is the most useful test for confirming the diagnosis of MS.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >1</FONT> MS lesions appear as areas of high signal, predominantly in the cerebral white matter or spinal cord, on T<FONT SIZE="1" COLOR="#660099" FACE="Arial" >2</FONT>-weighted images <I>(Figures 1 through 4). </I>MRI scanning is useful for detecting structural pathology in regions that can be difficult to image by computed tomography, such as the posterior fossa, craniocervical junction, and cervical cord.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >2</FONT> A brain MRI scan performed with a high-field magnet (1.5 tesla or greater) is abnormal in almost all patients who have clinically definite MS.</div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="589" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 567 WIDTH="193"><div> <IMG SRC="35cb9db0.jpg" border=0 width="185" height="219" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <B>Figure 1. </B>Fluid attenuation inversion recovery (FLAIR) sequence image of a transverse section from the brain of a patient with multiple sclerosis (MS). This image shows multiple high-signal periventricular and white-matter lesions. Although the FLAIR sequence is the most sensitive sequence for detecting MS lesions, it is not specific for demyelination.</div> </tD> <tD VALIGN=TOP WIDTH="193"><div> <IMG SRC="35db9b40.jpg" border=0 width="185" height="180" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <B>Figure 2. </B>FLAIR sequence image of a sagittal section from the brain of a patient with MS. Multiple high-signal white lesions (arrows) radiate from the surface of the lateral ventricles.</div> </tD> <tD VALIGN=TOP WIDTH="193"><div> <IMG SRC="35eb9b40.jpg" border=0 width="185" height="180" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <B>Figure 3. </B>Paired transverse MRI slices from the brain of a patient with MS. (Top) T<FONT SIZE="1" COLOR="#660099" FACE="Arial" >2</FONT>-weighted slices showing characteristic high-signal white-matter lesions (arrows) and revealing the burden of disease over time. (Bottom) T<FONT SIZE="1" COLOR="#660099" FACE="Arial" >1</FONT>-weighted slices, with gadolinium contrast enhancement of one of the lesions (arrow) indicating permeability of the blood-brain barrier. Enhancing lesions correlate pathologically with perivenular inflammation and are considered a surrogate marker of disease activity.</div> </tD> </tR> </TABLE></div> <div> <I>Sensory Evoked Potential Testing. </I>Evoked potentials (visual, brainstem auditory, and somatosensory) may be useful in demonstrating the presence of subclinical lesions in sensory pathways or in providing objective evidence of lesions suspected on the basis of subjective complaints.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >3</FONT> Of the sensory evoked potential tests, the visual evoked potential is the most useful because it can provide objective evidence of an optic nerve lesion that may not be evident on an MRI scan.</div> <div> <I>Cerebrospinal Fluid (CSF) Analysis. </I>In approximately 90 percent of patients with definite MS, the CSF IgG concentration is increased relative to other CSF proteins (e.g., albumin), and CSF gel electrophoresis reveals oligoclonal bands that are not present in a matched serum sample.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >4</FONT> However, an increased CSF IgG index and the presence of oligoclonal bands are not specific for MS and therefore are not diagnostic of the disease. CSF analysis probably is most useful for ruling out infectious or neoplastic conditions that mimic MS.</div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="567" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 896 WIDTH="563"><div> <IMG SRC="35f26090.jpg" border=0 width="550" height="777" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <B>Figure 4. </B>MRI scans of the spinal cord in a patient with MS. (Left) Sagittal images using the short tau inversion recovery (STIR) protocol reveal multiple high-signal lesions (arrows) within the spinal cord, consistent with demyelination. (Right) These lesions, which also can be seen on the transverse cuts, often are situated dorsolaterally, and are usually less than one vertebral body in length. The lesions rarely cause cord swelling.</div> </tD> </tR> </TABLE></div> <div> <I>Serologic Testing. </I>Peripheral blood tests may be helpful in excluding other disease processes. Testing frequently includes determination of the vitamin B<FONT SIZE="1" COLOR="#660099" FACE="Arial" >12</FONT> level, thyroid-stimulating hormone level, erythrocyte sedimentation rate, and anti-nuclear antibody titers, as well as a test for Lyme disease, and a test for syphilis (rapid plasma reagin test).</div> <div> In unusual cases, a more extensive evaluation may include tests for anti-neutrophil cytoplasmic antibodies, anti-phospholipid antibodies, Sjögren's syndrome A and B, angiotensin-converting enzyme, human T-lymphotrophic virus type I, and very long chain fatty acids (for adrenoleukodystrophy). Rarely, human immunodeficiency virus infection and opportunistic infections can mimic MS.</div> <div> diagnostic error</div> <div> Certain clinical or laboratory red flags should alert physicians to a possible diagnostic error.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >5</FONT> These flags include symptoms that could be explained by localized disease; the presence of steadily progressive disease; the absence of clinical remission; the absence of oculomotor, optic nerve, sensory, or bladder involvement; and normal CSF findings. However, none of these findings excludes the diagnosis of MS.</div> <div> Management</div> <div> symptomatic therapies</div> <div> <I>Spasticity. </I>Mild spasticity may be managed by stretching and exercise programs such as water therapy, yoga, and physical therapy. Medication is indicated when stiffness, spasms, or clonus interferes with function or sleep. Baclofen (Lioresal), tizanidine (Zanaflex), gabapentin (Neurontin), and benzodiazepines are effective antispastic agents<FONT SIZE="1" COLOR="#660099" FACE="Arial" >6</FONT> <I>(Table 4). </I>Intrathecal baclofen therapy has a major impact on medically intractable spasticity and has largely supplanted chemical rhizotomy or myelotomy.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >7</FONT></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="402" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 15 WIDTH="398"><div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 1018 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 18 WIDTH="387"><div> TABLE 4</div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 ><NOBR><div> <B>Symptomatic Therapies for Multiple Sclerosis</B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="387"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="387" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 879 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=BOTTOM HEIGHT= 18 WIDTH="81"><div> Symptom</div> </tD> <tD VALIGN=BOTTOM><NOBR><div> Therapy and possible adverse effects</div> </NOBR></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 159 ><NOBR><div> Spasticity</div> </NOBR></tD> <tD VALIGN=TOP WIDTH="300"><div> Baclofen (Lioresal), 10 to 40 mg three times daily; in high doses, can cause weakness and fatigue</div> <div> Tizanidine (Zanaflex), 2 to 8 mg three times daily; in high doses, can cause weakness and fatigue</div> <div> Gabapentin (Neurontin), 300 to 900 mg three or four times daily; in high doses, causes fatigue</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 176 WIDTH="81"><div> Pain and paroxysmal disorders</div> </tD> <tD VALIGN=TOP WIDTH="300"><div> Gabapentin, 300 to 900 mg three or four times daily; in high doses, causes fatigue</div> <div> Carbamazepine (Tegretol), 100 to 600 mg three times daily; in high doses, causes rash and neurologic side effects; requires monitoring of complete blood count and liver function</div> <div> Other anticonvulsants</div> <div> Amitriptyline (Elavil), 10 to 150 mg per day at bedtime</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 160 WIDTH="81"><div> Bladder urgency</div> </tD> <tD VALIGN=TOP WIDTH="300"><div> Oxybutynin (Ditropan), 5 mg once daily to 20 mg per day in divided doses; causes dry mouth and can exacerbate glaucoma or worsen urinary retention</div> <div> Tolterodine (Detrol), 2 to 4 mg twice daily; causes dry mouth and can exacerbate glaucoma or worsen urinary retention (these side effects occur less often than with oxybutynin)</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 177 ><NOBR><div> Depression</div> </NOBR></tD> <tD VALIGN=TOP WIDTH="300"><div> SSRIs preferred because of activating properties; can have sexual side effects</div> <div> Alternatives to SSRIs when sexual side effects occur: extended-release venlafaxine (Effexor) 75 to 225 mg per day, or sustained-release bupropion (Wellbutrin), 150 mg per day to 150 mg twice daily</div> <div> Third-line drug or for use when a patient has a sleep disorder or concomitant headaches: amitriptyline, 10 to 150 mg per day at bedtime</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 124 WIDTH="81"><div> Fatigue</div> </tD> <tD VALIGN=TOP WIDTH="300"><div> Amantadine (Symmetrel), 100 mg twice daily; can cause rash, edema, and anticholinergic effects</div> <div> Modafinil (Provigil), 100 to 200 mg given in the morning; can cause jittery sensation and palpitations</div> <div> SSRIs, can have sexual side effects</div> </tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="387"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="387" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 14 WIDTH="387"><div> SSRI = selective serotonin reuptake inhibitor.</div> </tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 15 WIDTH="398"><div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> </tR> </TABLE></div> <div> <I>Paroxysmal Disorders. </I>In most instances, dystonic spasms respond well to carbamazepine (Tegretol).<FONT SIZE="1" COLOR="#660099" FACE="Arial" >8</FONT> Paroxysmal pain can be treated effectively with anticonvulsants or amitriptyline (Elavil).<FONT SIZE="1" COLOR="#660099" FACE="Arial" >9</FONT></div> <div> <I>Bladder Dysfunction. </I>In patients with new bladder symptoms, urinalysis and culture should be performed to rule out infection, with appropriate treatment provided if needed. The first step in medical management of the neurogenic bladder is to determine whether the problem is a failure to empty urine or a failure to store urine. The history may or may not be helpful. A postvoid residual urinary volume is the best means of determining urinary retention.</div> <div> The anticholinergic drugs oxybutynin (Ditropan) and tolterodine (Detrol) are effective for symptoms of failure to store urine (in the absence of infection or overflow incontinence).<FONT SIZE="1" COLOR="#660099" FACE="Arial" >10</FONT></div> <div> Drug treatment of urinary retention usually is ineffective, although some patients benefit from attempts to decrease bladder neck tone using an alpha<FONT SIZE="1" COLOR="#660099" FACE="Arial" >1</FONT>-adrenergic receptor antagonist such as terazosin (Hytrin), doxazosin (Cardura), or tamsulosin (Flomax).<FONT SIZE="1" COLOR="#660099" FACE="Arial" >11</FONT> Bethanechol (Urecholine) may be helpful in patients with a flaccid bladder.</div> <div> Definitive treatment of urinary retention involves teaching the patient to perform intermittent self-catheterization, if possible. In some patients, inhaled desmopressin (DDAVP) can be used to suppress nocturnal urinary production.</div> <div> <I>Bowel Symptoms. </I>Constipation is common in patients with MS. It should be managed aggressively to avoid long-term complications.</div> <div> Fecal incontinence is rare; when it occurs, the addition of fiber can provide enough bulk to the stool to allow a partially incompetent sphincter to hold in the bowel movement long enough for the patient to reach a bathroom. Short-term use of anticholinergics or antidiarrheal agents may be effective in combating incontinence associated with diarrhea.</div> <div> <I>Sexual Symptoms. </I>A careful sexual history may reveal problems such as feelings of sexual inadequacy, impaired libido, or direct sexual dysfunction resulting from erectile dysfunction, impaired lubrication, spasticity, or heat-related sensory dysesthesias. Counseling, a review of the sexual side effects of medications, and medical therapy may be appropriate. In some patients with MS, erectile dysfunction can be managed effectively with sildenafil (Viagra).<FONT SIZE="1" COLOR="#660099" FACE="Arial" >12</FONT></div> <div> <I>Neurobehavioral Manifestations. </I>Depression occurs in more than one half of patients with MS.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >13</FONT> Patients with mild, transient depression can be cared for with supportive measures. Those with more severe depression should be treated with selective serotonin reuptake inhibitors (SSRIs), which are less sedating than other antidepressants. Bedtime administration of amitriptyline can be useful in depressed patients who also are having difficulty sleeping or have headaches or other pain syndromes.</div> <div> <I>Fatigue. </I>This symptom often responds to rest or medication. Amantadine (Symmetrel), 100 mg twice daily, may be effective.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >14</FONT> Modafinil (Provigil), a narcolepsy drug that acts as a CNS stimulant, has been found to be effective in patients with MS; the drug is given in a dosage of 200 mg once daily in the morning.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >15</FONT> Occasionally, SSRIs can relieve fatigue in patients with MS. Amantadine has the added advantage of having anti-influenza-A properties and may be given from October to March.</div> <div> relapses</div> <div> In a patient with an apparent relapse of MS, it is important to rule out a treatable infection such as sinusitis, bronchitis, or urinary tract infection.</div> <div> <I>Adrenal Corticosteroids. </I>Corticosteroids are the mainstay of symptomatic relief for an acute relapse of MS. These agents work through immunomodulatory and anti-inflammatory effects, restoration of the blood-brain barrier, and reduction of edema. They also may improve axonal conduction. Corticosteroid therapy shortens the duration of acute relapses and accelerates recovery. However, corticosteroids have not been shown to improve the overall degree of recovery or to alter the long-term course of MS.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >16</FONT></div> <div> If a patient is having acute disability from an attack, the physician should consider treatment with a three- to five-day course of intravenous methylprednisolone (or equivalent corticosteroid) in a dosage of 1 g administered intravenously in 100 mL of normal saline over 60 minutes once daily in the morning. </div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="119" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="LEFT" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 287 WIDTH="115"><div> Depression occurs in more than one half of patients with multiple sclerosis. Severe depression should be treated with SSRIs, which are less sedating than other antidepressants.</div> </tD> </tR> </TABLE></div> <div> <I>Other Treatments. </I>In patients with MS, physical therapy always should be considered because it improves function and quality of life independent of drug therapy.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >17</FONT> Supportive care in the form of counseling, occupational therapy, advice from social workers, input from nurses, and participation in patient support groups are all part of a united health care team approach to the management of MS. Some patients require temporary disability status.</div> <div> Patients with MS often are tempted to try alternative therapies such as special diets, vitamins, bee stings, a compound "off-label" transdermal medication (i.e., Prokarin), or acupuncture. Although definitive proof of the effectiveness of these treatments in MS is lacking, patients sometimes use them in a complementary fashion. Sole reliance on alternative therapies should be discouraged because patients then may be deprived of therapies that have been shown to be effective in the treatment of MS.</div> <div> disease-modifying therapies</div> <div> Four disease-modifying therapies for the initial management of MS are available in the United States: intramuscular interferon beta-1a (Avonex), subcutaneous interferon beta-1a (Rebif), interferon beta-1b (Betaseron), and glatiramer acetate (Copaxone). A fifth agent, mitoxantrone (Novantrone), has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of worsening forms of relapsing-remitting MS and secondary progressive MS <I>(Table 5).</I></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="402" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 15 WIDTH="398"><div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 883 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 18 WIDTH="387"><div> TABLE 5</div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 36 WIDTH="387"><div> <B>Immunomodulatory Drugs for the Treatment of Multiple Sclerosis</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="387"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="387" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 643 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=BOTTOM HEIGHT= 53 WIDTH="90"><div> <I>Drug</I></div> </tD> <tD VALIGN=BOTTOM WIDTH="65"><div> <I>Dosage</I></div> </tD> <tD VALIGN=BOTTOM WIDTH="146"><div> <I>Side effects and monitoring</I></div> </tD> <tD VALIGN=BOTTOM WIDTH="77"><div> <I>Cost for 1 month of treatment*</I></div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 76 WIDTH="90"><div> Interferon beta-1a (Avonex)</div> </tD> <tD VALIGN=TOP WIDTH="65"><div> 30 mcg IM once weekly</div> </tD> <tD VALIGN=TOP WIDTH="146"><div> Influenza-like symptoms</div> <div> Monitoring of CBC and liver function</div> </tD> <tD VALIGN=TOP WIDTH="77"><div> $1,278</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 114 WIDTH="90"><div> Interferon beta-1a (Rebif)</div> </tD> <tD VALIGN=TOP WIDTH="65"><div> 22 to 44 mcg SC three times weekly</div> </tD> <tD VALIGN=TOP WIDTH="146"><div> Influenza-like symptoms and injection-site reactions</div> <div> Monitoring of CBC and liver function</div> </tD> <tD VALIGN=TOP WIDTH="77"><div> 1,517</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 114 WIDTH="90"><div> Interferon beta-1b (Betaseron)</div> </tD> <tD VALIGN=TOP WIDTH="65"><div> 0.25 mg SC every other day</div> </tD> <tD VALIGN=TOP WIDTH="146"><div> Influenza-like symptoms and injection-site reactions</div> <div> Monitoring of CBC and liver function</div> </tD> <tD VALIGN=TOP WIDTH="77"><div> 1,403</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 114 WIDTH="90"><div> Glatiramer (Copaxone)</div> </tD> <tD VALIGN=TOP WIDTH="65"><div> 20 mg SC once daily</div> </tD> <tD VALIGN=TOP WIDTH="146"><div> Injection-site reactions and, rarely, a benign systemic reaction</div> <div> Requires no blood monitoring</div> </tD> <tD VALIGN=TOP WIDTH="77"><div> 1,261</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 107 WIDTH="90"><div> Mitoxantrone (Novantrone)</div> </tD> <tD VALIGN=TOP WIDTH="65"><div> 5 to 12 mg per m<FONT SIZE="1" COLOR="#660099" FACE="Arial" >2</FONT> IV every 3 months</div> </tD> <tD VALIGN=TOP WIDTH="146"><div> Mild chemotherapy-related side effects, cumulative cardiotoxicity, small increased risk of leukemia</div> </tD> <tD VALIGN=TOP WIDTH="77"><div> 1,453 </div> </tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="387"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="387" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 96 WIDTH="387"><div> IM = intramuscular; CBC = complete blood count; SC = subcutaneous; IV = intravenous.</div> <div> *-Estimated cost to the pharmacist (rounded to the nearest dollar) for the lowest given dosage, based on average wholesale prices in Red book. Montvale, N.J.: Medical Economics Data, 2004. Cost to the patient will be higher, depending on prescription filling fee.</div> <div>  </div> </tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 15 WIDTH="398"><div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> </tR> </TABLE></div> <div> <I>Beta Interferons. </I>The beta interferons are naturally occurring cytokines with a variety of immunomodulating and antiviral activities that may account for their therapeutic effects. The three FDA-approved beta interferons that are used for MS have been shown to reduce relapses by about one third and are recommended as first-line therapy or for use in glatiramer-intolerant patients who have relapsing-remitting MS.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >18</FONT> In randomized, double-blind placebo-controlled trials,<FONT SIZE="1" COLOR="#660099" FACE="Arial" >19-21</FONT> use of beta interferons resulted in a 50 to 80 percent reduction in inflammatory lesions visualized on brain MRI scans. There also is evidence that these drugs improve quality of life and cognitive function.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >22,23</FONT></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="119" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="LEFT" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 344 WIDTH="115"><div> Corticosteroid therapy shortens the duration of acute relapses of multiple sclerosis and accelerates recovery. However, corticosteroids have not been definitely shown to improve the overall degree of recovery or to alter the long-term course of the disease.</div> </tD> </tR> </TABLE></div> <div> The major difference in the beta interferon drugs is that intramuscular interferon beta-1a is given once a week and subcutaneous interferon beta-1a and interferon beta-1b are given three times a week, or every other day, respectively. The adequacy of weekly dosing has been questioned.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >24,25</FONT> There appears to be a modest dose-response effect with the beta interferons.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >24</FONT> One study<FONT SIZE="1" COLOR="#660099" FACE="Arial" >26</FONT> of double-dose (60-mcg) intramuscular interferon beta-1a administered once a week found no benefit over the single-dose regimen. Whether the benefit of more frequent dosing is sustained remains unclear. An increased incidence of neutralizing antibodies with the more frequent subcutaneous dosing also must be considered.</div> <div> Influenza-like symptoms, including fever, chills, malaise, muscle aches, and fatigue, occur in approximately 60 percent of patients treated with interferon beta-1a or interferon beta-1b. These symptoms usually dissipate with continued therapy and premedication with a nonsteroidal anti-inflammatory drug. Dose titration at the initiation of beta interferon therapy also is a useful strategy.</div> <div> Other side effects of the beta interferons include injection-site reactions, worsening of pre-existing spasticity, depression, mild anemia, thrombocytopenia, and elevated transaminase levels. These side effects usually are not severe and rarely lead to discontinuation of treatment.</div> <div> Treatment with any beta interferon can result in the development of neutralizing antibodies. Although study results are variable, once-weekly intramuscular interferon beta-1a therapy has been reported to have the lowest incidence of neutralizing antibody development.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >27</FONT> The effect of neutralizing antibodies on the long-term efficacy of beta interferon therapy remains to be fully defined because titers and durations of antibody positivity (some neutralizing antibodies resolve with time) are variable.</div> <div> <I>Glatiramer. </I>This drug is a polypeptide mixture that was originally designed to mimic and compete with myelin basic protein. Its mechanism of action is distinct from that of the beta interferons; therefore, patients may respond differently to the drug. Glatiramer in a dosage of 20 mg administered subcutaneously once daily has been shown to reduce the frequency of MS relapses by approximately one third. The drug also is recommended as a first-line treatment in patients with relapsing-remitting MS and in the treatment of patients who cannot tolerate beta interferon therapy.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >28</FONT> Glatiramer therapy results in a one-third reduction in the inflammatory activity seen on MRI scans.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >29</FONT></div> <div> Glatiramer generally is well tolerated and is not associated with influenza-like symptoms.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >30</FONT> Immediate postinjection reactions include local inflammation and an uncommon idiosyncratic reaction consisting of flushing, chest tightness with palpitations, anxiety, or dyspnea, which resolves spontaneously without sequelae. Routine laboratory monitoring is not considered necessary in patients treated with glatiramer, and the development of binding antibodies does not interfere with therapeutic efficacy.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >31</FONT></div> <div> <I>Mitoxantrone. </I>A phase-III, randomized, placebo-controlled, multicenter trial<FONT SIZE="1" COLOR="#660099" FACE="Arial" >32</FONT> found that mitoxantrone, an anthracenedione antineoplastic agent, reduced the number of treated MS relapses by 67 percent and slowed progression on the Expanded Disability Status Scale, Ambulation Index, and MRI measures of disease activity. Mitoxantrone is recommended for use in patients with worsening forms of MS.</div> <div> Acute side effects of mitoxantrone include nausea and alopecia. Because of cumulative cardiotoxicity, the drug can be used for only two to three years (or for a cumulative dose of 120 to 140 mg per m<FONT SIZE="1" COLOR="#660099" FACE="Arial" >2</FONT>). There also is some concern about treatment-related leukemia. Mitoxantrone is a chemotherapeutic agent that should be prescribed and administered only by experienced health care professionals.</div> <div> new and other drugs</div> <div> Natalizumab (Antegren) is in the final stages of phase-III clinical trails and is under accelerated review by the FDA. In a phase-II clinical trial,<FONT SIZE="1" COLOR="#660099" FACE="Arial" >33</FONT> this drug appeared promising in that it reduced active MRI lesions by 90 percent and decreased MS relapses by more than 50 percent. Natalizumab is a monoclonal antibody that is directed against an adhesion molecule called VLA-4. The drug is administered intravenously once a month.</div> <div> Despite lack of FDA approval and definitive evidence of efficacy, several other drugs commonly are used in patients with MS. A number of small clinical trials<FONT SIZE="1" COLOR="#660099" FACE="Arial" >34-38</FONT> support the modest effect of intravenous IgG, azathioprine, methotrexate, and cyclophosphamide, either alone or in combination with standard therapy.</div> <div> Initiation of Early Therapy</div> <div> Accumulating evidence indicates that the best time to initiate disease-modifying treatment is early in the course of MS.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >39</FONT> Data indicate that irreversible axonal damage may occur early in relapsing-remitting MS,<FONT SIZE="1" COLOR="#660099" FACE="Arial" >40</FONT> and that drug therapies appear to be more effective in preventing new lesion formation than in repairing old lesions. With disease progression, the autoimmune response of the disease may become more difficult to suppress. Both intramuscular interferon beta-1a therapy and subcutaneous interferon beta-1a therapy have been shown to reduce the cumulative probability of the development of clinically definite MS in patients who present with a first clinical demyelinating episode and have two or more brain lesions on an MRI scan.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >41,42</FONT> Based on these data, the National Multiple Sclerosis Society<FONT SIZE="1" COLOR="#660099" FACE="Arial" >43</FONT> supports the initiation of immunomodulating therapy at the time of diagnosis. </div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="119" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="LEFT" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 172 WIDTH="115"><div> Evidence is accumulating that disease-modifying drug therapy should be initiated early in the course of multiple sclerosis.</div> </tD> </tR> </TABLE></div> <div> The physician must weigh evidence and recommendations against the practical concerns of young patients for whom the prospect of starting therapy that requires self-injection may be frightening and burdensome. Furthermore, few long-term data (more than 10 years) are available on the safety and sustained efficacy of disease-modifying drugs. A patient may opt to defer therapy, hoping to be among the minority of persons with benign MS; however, certain MRI and clinical features should prompt the physician and patient to reconsider this approach.</div> <div> An MRI scan with contrast-enhancing lesions, a large burden of white matter disease, or any T<FONT SIZE="1" COLOR="#660099" FACE="Arial" >1</FONT> low-signal lesions (black holes) suggests a relatively poor prognosis.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >44</FONT> It may be useful to repeat brain MRI scanning in six months or one year to determine how quickly the disease process is evolving. The presence of spinal cord lesions or atrophy also suggests a poor prognosis. Clinical features may be less useful for assessing prognosis. Once definite disability develops, it may be too late to treat that component of the disease.</div> <div> The ability to diagnose and treat MS has improved considerably in the past 10 years because of the availability of MRI and partially effective immunomodulating therapies. The limited efficacy of immunomodulating drugs in the later, noninflammatory stages of MS highlights the importance of developing remyelinating and neuroprotective strategies for the disease.</div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="408" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 675 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="387"><div> <B>Strength of Recommendations</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="387"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="387" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="391" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 591 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="390" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=BOTTOM HEIGHT= 20 ><NOBR><div> <B>Key clinical recommendation</B></div> </NOBR></tD> <tD VALIGN=BOTTOM><NOBR><div> <B>Label</B></div> </NOBR></tD> <tD VALIGN=BOTTOM><NOBR><div> <B>References</B></div> </NOBR></tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="390" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 76 WIDTH="284"><div> Magnetic resonance imaging should be performed or repeated three months after a clinically suspicious episode to facilitate early diagnosis of MS.</div> </tD> <tD VALIGN=TOP WIDTH="31"><div> C</div> </tD> <tD VALIGN=TOP WIDTH="65"><div> 1</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="390" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 57 WIDTH="284"><div> Corticosteroid therapy should be used to shorten the duration of MS relapses and accelerate recovery.</div> </tD> <tD VALIGN=TOP WIDTH="31"><div> A</div> </tD> <tD VALIGN=TOP WIDTH="65"><div> 16</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="390" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 57 WIDTH="284"><div> Disease-modifying treatment should be started early in the course of MS to minimize irreversible axonal damage.</div> </tD> <tD VALIGN=TOP WIDTH="31"><div> C</div> </tD> <tD VALIGN=TOP WIDTH="65"><div> 35</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="390" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 96 WIDTH="284"><div> Glatiramer and the beta interferons have different mechanisms of action. Patients with MS who have an unsatisfactory response to beta interferons should be considered for glatiramer therapy.</div> </tD> <tD VALIGN=TOP WIDTH="31"><div> C</div> </tD> <tD VALIGN=TOP WIDTH="65"><div> 23</div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="390" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 107 WIDTH="284"><div> Patients with worsening forms of MS may be referred for mitoxantrone therapy; however, this agent has acute short-term adverse effects, as well as serious long-term adverse effects that include cardiotoxicity.</div> </tD> <tD VALIGN=TOP WIDTH="31"><div> B </div> </tD> <tD VALIGN=TOP WIDTH="65"><div> 26 </div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="388" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 106 WIDTH="384"><div> MS = multiple sclerosis.</div> <div> A = consistent, good quality patient-oriented evidence; B = inconsistent or limited quality patient-oriented evidence;</div> <div> C = consensus, disease-oriented evidence, usual practice, opinion, or case series. See page 1845 for more information.</div> </tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> </TABLE></div> <div> The author indicates that he does not have any conflicts of interest. Sources of funding: Dr. Calabresi has received research support or honoraria as a consultant or speaker for Berlex Laboratories, Biogen, Inc., IDEC Pharmaceuticals, Immunex Corporation, Serono, Inc., and Teva Neuroscience, Inc.</div> <bR> <div> The Author</div> <div> PETER A. CALABRESI, M.D., is associate professor of neurology at Johns Hopkins University School of Medicine, Baltimore. Dr. Calabresi received his medical degree from Brown University School of Medicine, Providence, R.I., and completed a residency in neurology at Strong Memorial Hospital, Rochester, N.Y., where he served as chief resident. He also was a clinical associate and research fellow in the Neuroimmunology Branch of the National Institutes of Health, Bethesda, Md. 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Fischer JS, Priore RL, Jacobs LD, Cookfair DL, Rudick RA, Herndon RM, et al. Neuropsychological effects of interferon beta-1a in relapsing multiple sclerosis. Multiple Sclerosis Collaborative Research Group. Ann Neurol 2000;48:885-92.</div> <div> 24. Panitch H, Goodin DS, Francis G, Chang P, Coyle PK, O'Connor P, et al. Randomized, comparative study of interferon beta-1a treatment regimens in MS: the EVIDENCE Trial. Neurology 2002;59:1496-506.</div> <div> 25. Durelli L, Verdun E, Barbero P, Bergui M, Versino E, Ghezzi A, et al. Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN). Lancet 2002;359:1453-60.</div> <div> 26. Double-blind randomized multicenter dose-comparison study of interferon-beta-1a (AVONEX): rationale, design and baseline data. Mult Scler 2001;7:179-83.</div> <div> 27. Bertolotto A, Malucchi S, Sala A, Orefice G, Carrieri PB, Capobianco M, et al. Differential effects of three interferon betas on neutralising antibodies in patients with multiple sclerosis: a follow up study in an independent laboratory. J Neurol Neurosurg Psychiatry 2002;73:148-53.</div> <div> 28. Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, et al. Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Copolymer 1 Multiple Sclerosis Study Group. Neurology 1998;50:701-8.</div> <div> 29. Comi G, Filippi M, Wolinsky JS. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging-measured disease activity and burden in patients with relapsing multiple sclerosis. European/Canadian Glatiramer Acetate Study Group. Ann Neurol 2001;49:290-7.</div> <div> 30. Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 1995;45:1268-76.</div> <div> 31. Brenner T, Arnon R, Sela M, Abramsky O, Meiner Z, Riven-Kreitman R, et al. Humoral and cellular immune responses to Copolymer 1 in multiple sclerosis patients treated with Copaxone. J Neuroimmunol 2001;115:152-60.</div> <div> 32. Hartung HP, Gonsette R, Konig N, Kwiecinski H, Guseo A, Morrissey SP, et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 2002;360:2018-25.</div> <div> 33. Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GP, Libonati MA, et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2003;348:15-23.</div> <div> 34. Achiron A, Gabbay U, Gilad R, Hassin-Baer S, Barak Y, Gornish M, et al. Intravenous immunoglobulin treatment in multiple sclerosis. Effect on relapses. Neurology 1998;50:398-402.</div> <div> 35. Yudkin PL, Ellison GW, Ghezzi A, Goodkin DE, Hughes RA, McPherson K, et al. Overview of azathioprine treatment in multiple sclerosis. Lancet 1991;338:1051-5.</div> <div> 36. Goodkin DE, Rudick RA, VanderBrug Medendorp S, Daughtry MM, Schwetz KM, Fischer J, et al. Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. Ann Neurol 1995;37:30-40.</div> <div> 37. Calabresi PA, Wilterdink JL, Rogg JM, Mills P, Webb A, Whartenby KA. An open-label trial of combination therapy with interferon beta-1a and oral methotrexate in MS. Neurology 2002;58:314-7.</div> <div> 38. Weiner HL, Cohen JA. Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects. Mult Scler 2002;8:142-54.</div> <div> 39. Coyle PK, Hartung HP. Use of interferon beta in multiple sclerosis: rationale for early treatment and evidence for dose- and frequency-dependent effects on clinical response. Mult Scler 2002;8:2-9.</div> <div> 40. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998;338:278-85.</div> <div> 41. Jacobs LD, Beck RW, Simon JH, Kinkel RP, Brownscheidle CM, Murray TJ, et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 2000;343:898-904.</div> <div> 42. Comi G, Filippi M, Barkhof F, Durelli L, Edan G, Fernandex O, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001;357:1576-82.</div> <div> 43. National Multiple Sclerosis Society. Disease management consensus statement. Accessed online September 1, 2004, at http://www.nationalmssociety.org/pdf/forpros/Exp_Consensus.pdf.</div> <div> 44. Filippi M, Grossman RI. MRI techniques to monitor MS evolution: the present and the future. Neurology 2002;58:1147-53.</div> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="369" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 229 WIDTH="365"><div> Copyright © 2004 by the American Academy of Family Physicians.</div> <div> This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact <FONT SIZE="3" COLOR="#004A8A" FACE="Arial" ><A HREF="mailto:afpserv@aafp.org" TARGET="_top" TITLE="mailto:afpserv@aafp.org"><U><U>afpserv@aafp.org</U></U></A></FONT> for copyright questions and/or permission requests.</div> </tD> </tR> </TABLE></div> <bR> <DIV ALIGN="LEFT"></DIV> <div> <A HREF="http://www.aafp.org/afp/20041115/contents.html" TARGET="_top" TITLE="http://www.aafp.org/afp/20041115/content"><U><U>November 15, 2004 Contents</U></U></A><FONT SIZE="2" COLOR="#660099" FACE="Arial" > | </FONT><A HREF="http://www.aafp.org/afp" TARGET="_top" TITLE="http://www.aafp.org/afp"><U><I><U>AFP</U></I></U></A><A HREF="http://www.aafp.org/afp" TARGET="_top" TITLE="http://www.aafp.org/afp"><U><U> Home Page</U></U></A><FONT SIZE="2" COLOR="#660099" FACE="Arial" > | </FONT><A HREF="/" TARGET="_top" TITLE="/"><U><U>AAFP Home</U></U></A><FONT SIZE="2" COLOR="#660099" FACE="Arial" > | </FONT><A HREF="http://search.aafp.org/" TARGET="_top" TITLE="http://search.aafp.org/"><U><U>Search</U></U></A></div> <bR> <div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFFF WIDTH="17"><div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> <tD VALIGN=TOP BGCOLOR=#FFFFFF><NOBR><div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="28" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 21 WIDTH="24"><div> <IMG SRC="36610100.jpg" border=0 width="16" height="16" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 21 WIDTH="24"><div> <IMG SRC="36710100.jpg" border=0 width="16" height="16" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> </tR> </TABLE></div> <bR> <DIV ALIGN="LEFT"></DIV> <div> <IMG SRC="35104040.png" border=0 width="4" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </NOBR></tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> </TABLE></div> <bR> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="369" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 57 WIDTH="365"><div> <B>Patients with Multiple Sclerosis May Want to Take Wait-And-See Approach to Medications</B></div> <bR> </tD> </tR> </TABLE></div> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="369" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="365"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="365" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="369" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 2447 WIDTH="365"><div> <I><B> <A NAME="patients_with_multiple_sclerosis_may"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B></I><I><B>"Patients with Multiple Sclerosis May Want to Take Wait-And-See Approach to Medications"</B></I></div> <bR> <bR> <div> ROCHESTER, MN -- August 31, 2004 -- Rather than taking medication to ward off a future potential attack, patients diagnosed with multiple sclerosis (MS) may want to take a conservative approach and wait watchfully with their doctors for the first few years to see how the disease progresses over time, according to a new Mayo Clinic study published in the August Annals of Neurology (http://www3.interscience.wiley.com/cgi-bin/jhome/76507645). "Our study demonstrates that the longer the duration of MS and the lower the disability, the more likely a patient is to remain stable and not progress to a greater level of disability," says Sean Pittock, M.D., lead author of the paper. "This isn't a small issue; it's a big issue." Moses Rodriguez, M.D., Mayo Clinic neurologist and senior author of the paper, adds, "The documentation of benign MS does exist, and this condition can be identified during an analysis of the patient at even five years with MS." The investigators propose a definition of benign MS as patients who have MS for 10 years or more who have an Expanded Disability Status Scale (EDSS) score of 2 or less, because they have less than 10 percent likelihood of developing significant disability in the future. The EDSS quantifies the amount of disability in MS patients from zero (normal neurological exam) to 10 (death due to MS). On this scale, a score of 2 indicates minimal disability, 4 indicates moderate disability but able to walk unassisted, 6 indicates requirement of an aid or cane to walk, and 8 indicates need for a wheelchair. Patients who have benign MS can have ongoing attacks, but they do not accrue any disability from the attacks, says Dr. Rodriguez. "You have symptoms, but they go away, and if they come back, they go away again, typically after a week or so. You might have a bad week or an attack -- like the loss of vision in one eye -- but you completely recover. Most of the time, however, there would be no outward sign of the disease, and the patients themselves would say that they are normal." Drs. Pittock, Rodriguez and colleagues found that only 7 percent of patients who had minimal or no disability (EDSS score equal to or less than 2) after 10 years with MS progressed to a greater level of disability (EDSS score greater than 4), and none needed a wheelchair after 20 years with MS. However, for those MS patients studied who had an EDSS score of 2.5 to 4 after 10 years of the disease, 12 of 21 patients' disabilities increased to a score greater than 4 after 20 years with the disease. Another Mayo Clinic neurologist and author, Brian Weinshenker, M.D., says of the study: "This confirms some other studies, but it flies in the face of the commonly held belief that MS is never benign and that every person should be started on lifelong interferon therapy before we get a feel of how the natural course of their illness will behave." The investigators indicate that this news is particularly important for patients who have had benign MS for 10 years or longer, for whom physicians can make a reasonable prediction that they will not develop progressive disability. However, forecasting the course of a patient's MS prior to the five-year mark remains difficult, the investigators indicate. These findings have potential impact for the 17 percent of all U.S. multiple sclerosis patients who have benign disease. Dr. Rodriguez indicates that this percentage represents as many as approximately 70,000 benign MS patients, assuming the total of MS patients in the United States to be 400,000. The current approach prevalent in the MS treatment community to prescribing drugs for MS patients is "the earlier the better," according to Drs. Rodriguez and Pittock. "There is an overwhelming drive to start all patients with a diagnosis of MS on immunomodulatory medications," says Dr. Pittock. However, the Mayo Clinic study calls this drive into question. "This study raises questions about the current dogma out there that all patients should be started on medications as soon as possible," says Dr. Rodriguez. "If we treat everyone early, we would treat some people who never needed treatment. And, if they don't need treatment, we can save society hundreds of millions of dollars, and the patients with benign MS can avoid major side effects." Dr. Rodriguez elaborates on the costs, monetary and physical, of prescribing medications to MS patients who may turn out to have benign disease. "Medications are expensive, about $10,000 per year," he says. "The injections [of immunomodulatory medications] are painful, and they cause side effects like nausea, vomiting, fatigue, and achiness. You may have to lie down in bed for the day. It can be like having the flu every day of your life. In addition, the drugs are only partly effective, and their effectiveness over the long course of the disease has not been demonstrated." Mayo Clinic Department of Neurology's philosophy in working with MS patients is to share the therapeutic decision-making process between physician and patient, weighing the pros and cons of starting medication with the predictive data on hand, as well as the patient's personality and personal wishes, to arrive at a customized determination of appropriate treatment for each patient. The investigators on this study believe that their findings will be helpful in this process. Though the concept of benign MS is not new, the study represented in August Annals of Neurology manuscript is the most extensive population study of MS to date, says Dr. Rodriguez. The Olmsted County population of MS patients has been studied since 1905. The study included all people in the population, not just those who sought a doctor for MS. This is notable in that patients who have benign MS may not seek medical attention. For MS patients who have concerns or questions regarding whether they have benign MS or whether they should be on immunomodulatory medications, Dr. Rodriguez stresses that it is important for them to contact their personal physicians to discuss their diseases and make decisions customized to their personal situations. SOURCE: Mayo Clinic </div> <bR> </tD> </tR> </TABLE></div> <bR> <div> <B>Making the Decision to Use a Disease-Modifying Drug</B></div> <div> <B>Putting the Brakes on MS</B></div> <div> <B>Making the Decision to Use a Disease-Modifying Drug</B></div> <div> by Lorna Smedman</div> <div> <B>PART I: THE START OF SOMETHING NEW</B></div> <div> The world of MS changed in 1993. That year, the FDA approved a new drug that had shown it could influence—or modify—the expected course of relapsing-remitting MS. The drug was a type of interferon, with the trade name Betaseron. Relapsing-remitting MS is the most common type of MS when people are first diagnosed. It has periods of attacks, when symptoms are severe, followed by quiet periods when symptoms resolve.</div> <div> By the end of 2002, four new MS drugs had been approved: <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Avonex</U></FONT> (interferon beta-1a), <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Betaseron</U></FONT> (interferon beta-1b), <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Copaxone</U></FONT> (glatiramer acetate); and <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Rebif</U></FONT> (interferon beta-1a). The four “disease-modifying drugs” share many characteristics.</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" >Each is used regularly, at intervals ranging from once a day to once a week, on an on-going basis.</FONT></div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" >Each is injected, most often by the individual with MS or by a nonprofessional care partner.</FONT></div> <div> <FONT SIZE="3" COLOR="#660099" FACE="Symbol" >·</FONT><FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT>Each has demonstrated in well-conducted clinical trials an ability to decrease the number of exacerbations a person with relapsing MS would expect to have. An exacerbation—which is also called an attack, a relapse, or a flare—is a sudden worsening of MS symptoms, or the appearance of new MS symptoms, <B>which lasts at least 24 hours</B> and is separated from a previous attack by at least one month of relative stability or wellness.</div> <div> Last, but perhaps most important:</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" >Each can calm invisible, or “silent”, MS by about the same percentage, reducing the number of MS lesions, or areas of damage, in the brain or spinal cord, that occur normally in untreated MS.</FONT></div> <div> Silent lesions are not linked directly to any symptoms. People are unaware of them. They don’t feel anything. However, over time, individuals with more and larger lesions almost always have more severe MS disability.</div> <div> Most MS specialists believe there is a powerful connection between reducing the size and number of these lesions and the ability to slow or stop the losses of ability that accompany MS over the long term. These losses include (but aren’t limited to) weakness, fatigue, tremor, problems with walking, balance, coordination, dexterity, clear thinking and decision-making, vision, sexual function, and bladder control.</div> <div> In other words these medications are thought to slow down the development of MS disability.</div> <div> More than half of all the people who begin with a relapsing-remitting MS that gets better in the periods between attacks, develop secondary-progressive MS eventually. Then they have fewer attacks, or even no attacks, but slowly the MS worsens and they tend to become more disabled.</div> <div> In 2000, a different drug—<FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Novantrone</U></FONT> (mitoxantrone)—was approved for relapsing-remitting MS that is worsening rapidly <B>and</B> for secondary-progressive MS.</div> <div> Novantrone is not taken regularly via injections at home. It must be administered by a doctor or other medical professional as an IV infusion, usually once every three months. It is an immune suppressant, while the others are considered immune modulators (or modifiers). Like the other four drugs, it calms “silent” MS, reduces the number of attacks, and delays the onset of more disability. In fact, it reduces lesion formation more effectively than the other disease-modifying drugs.</div> <div> Because of potential heart damage, which is a side effect of this medication, Novantrone treatment is generally limited to three years.</div> <div> <B>Multiple sclerosis is treatable</B></div> <div> None of these five drugs will cure MS. They cannot stop the disease totally. Much remains to be learned about the best ways to use them, and how to tell if an individual is getting the maximum benefit. Trials of various kinds are in progress to see if the benefits can be increased, and, in the case of Novantrone, the side effects lessened.</div> <div> As you will see from some people who take these medications, they are not always easy to stay with.</div> <div> But these drugs end forever the age when people with MS were told, “no treatment available.” For the great majority of people diagnosed in the 21st century, MS can be modified and partially controlled. Scientists believe the outlook will be brighter still as more is learned and new agents are developed.</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>Additional uses—earlier and later</B></FONT></div> <div> In 2003, the <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>FDA extended labeling of Avonex</U></FONT> to include individuals who have experienced a single attack of MS symptoms, provided they also have MRI results that show brain lesions that are consistent with MS. The early use of the medication is strongly associated with a delay in a second attack.</div> <div> In the same year, <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Betaseron’s label was extended</U></FONT> to cover people with all relapsing forms of MS, including secondary-progressive MS if the person still experiences attacks.</div> <div> <B>Playing by the new rules</B></div> <div> We asked some people with MS to share stories of their life with MS in the new era of disease-modifying drugs. Steve, Mimi, Joey, Maggie, Marla, and Evelyn have each had different experiences as they faced some of</div> <div> the common problems. The first issue is the decision to begin.</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>Steve Paddison’s decision</B></FONT></div> <div> Everything was right on schedule for Steve Paddison in 1996. At 29, he had finished his master’s degree and had been hired to teach at an elementary school in Virginia. Then he had a second MS attack and lost sight in his right eye. His neurologist confirmed MS and recommended treatment right away.</div> <div> Steve got a second opinion from a well-known neurologist who had a great deal of expertise with MS—his father. Dr. Richard Paddison had been head of the neurology department at Louisiana State University for 20 years, and was a former medical advisor for the National MS Society.</div> <div> Steve Paddison has been taking Avonex since 1996. He credits the treatment for keeping his MS in check. Staying with his injections makes him feel more in charge of his life, and gives him some peace of mind. The decision to start was not difficult for him. He had confidence in the recommendations. He began with a positive attitude that has not flagged. But not everyone comes to the decision so easily.</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>Mimi Mosher’s struggle</B></FONT></div> <div> Mimi Mosher has seven siblings, and they have given her a “gazillion” suggestions about how to treat her MS. She began experiencing her first symptoms at age 24. For a long time she had no diagnosis. Her doctor only said she “might” have MS. Then, in 1993, her gait problems became much worse, and her diagnosis was confirmed.</div> <div> She made changes in her diet. She incorporated exercise and meditation into her life. She even experimented with unproven bee venom therapy. Even so, Mimi continued to hope that her problems would turn out to be something else, not MS.</div> <div> Accepting an MS diagnosis is never easy. Denial, anger, fear, and grief are common reactions as people struggle to understand the strange things that are happening to their bodies, emotions, and minds. In the past, MS specialists often asserted that a little denial was not necessarily bad. After all, denial allows people to keep going. Denial creates a cushion of time during which a person can absorb the impact of having MS and gradually come to terms with the changes it is bringing.</div> <div> Today, experts advise starting treatment as soon as possible—immediately following a diagnosis of relapsing MS, or earlier still, following “clinically isolated syndrome” (or CIS), when an attack of MS symptoms is accompanied by a positive MRI scan. Research strongly suggests that early treatment leads to better outcomes. The cushion of denial isn’t the same anymore.</div> <div> Back in 1994, a year after her diagnosis, Mimi Mosher was hearing about the new MS drug called Betaseron. She was interested, but her doctor advised against it. He thought her symptoms were not severe enough to warrant what he saw as a major treatment.</div> <div> Mimi was glad to hear this. The idea of injections was frightening. It also bothered her that this medication wouldn’t cure her MS, only slow it down. After a severe exacerbation later that year, she decided to give Betaseron a try.</div> <div> After a year, she stopped. During that year she had had no attacks, but she couldn’t stop wondering if she would have been free of attacks without taking the drug. She found it hard to trust her medication since no one could explain exactly how it worked.</div> <div> Today she feels that her “experiment,” as she calls her decision to stop therapy, was a mistake. After stopping, her symptoms gradually returned, until Mimi found herself “wall-walking” and using a cane once again. She decided to go back on therapy, choosing Avonex for her second try.</div> <div> Today, Mimi believes people with relapsing MS should consider a disease-modifying drug right away. Many of the issues she worried about have diminished with time and experience. Her MS has worsened somewhat but she will continue taking injections, knowing that she’s doing something more positive than “crossing my fingers and hoping that my symptoms won’t get too much worse.”</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>A new recommendation for treating relapsing MS</B></FONT></div> <div> In the spring of 1998, the National Multiple Sclerosis Society’s Medical Advisory Board broke a 50-year tradition by recommending a specific treatment. A task force of MS experts reviewed all available scientific and clinical trial data, including evidence from MRI studies. They also considered their own clinical experience treating people with MS with disease-modifying drugs. The task force decided that the evidence of beneficial effects was overwhelming.</div> <div> To help all the people with MS like Mimi, and their concerned physicians, the Society published the <B>Disease Management Consensus Statement</B>. It said that people who have been diagnosed with relapsing-remitting MS should consider treatment as soon as possible—and continue treatment indefinitely. The 1998 statement was updated in 2002.</div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="638" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 303 WIDTH="634"><div> <B>Main Points of the Revised Consensus Statement, October, 2002</B></div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" >Avonex, Betaseron, Rebif, Novantrone, and Copaxone reduce future disability and improve the quality of life for many people with relapsing forms of MS.</FONT></div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" >Therapy should begin as soon as possible following a definite diagnosis of MS and determination of a relapsing course.</FONT></div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" >Access to the therapy should not be limited by level of disability, age, or the frequency of relapses.</FONT></div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" >Most concurrent medical conditions do not mean that any of these four therapies should be avoided.</FONT></div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" >Therapy should be continued indefinitely, unless there is a clear lack of benefit, intolerable side effects, new data that reveal other reasons for stopping, or a better therapy becomes available. Therapy should not be discontinued during reevaluation for continuing treatment.</FONT></div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" >All these agents should be included in formularies (lists of approved drugs) and covered by third-party payers. The choice of drug should be made jointly by the individual and her or his physician, based on professional evaluation and individual preferences. Movement from one drug to another should be permitted.</FONT></div> </tD> </tR> </TABLE></div> <DIV ALIGN="LEFT"></DIV> <div> The complete 2002 <B>Disease Management Consensus Statement</B> is available at every Society chapter. Phone 1-800-FIGHT-MS (1-800-344-4867) to be connected to the office nearest you. The text is also on the Society Web site at <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>www.nationalmssociety.org/Sourcebook-Early.asp</U></FONT>.</div> <div> Evidence for all current treatments is summed up in <B>Disease Modifying Therapies in Multiple Sclerosis; Evidence-Based Management Strategies for Disease Modifying Therapies in Multiple Sclerosis</B>, a 58-page clinical practice guideline from the MS Council for Clinical Practice Guidelines. It can be downloaded for free at <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>www.pva.aa.psiweb.com/NEWPVASITE/ publications/pubs/msdmt_cpg.htm</U></FONT>.</div> <div> The Society encourages all people with MS to discuss treatment options with their health-care practitioners, and to make sure their doctor or neurologist is aware of the National MS Society’s Consensus Statement.</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>Joey Rowland’s solutions</B></FONT></div> <div> Steve Paddison’s story is representative of the new possibilities for putting the brakes on MS. Short of finding a cure, approval of these drugs has been the most promising breakthrough in the history of this disease.</div> <div> Joey Rowland of Southern California was skeptical about placing much faith in drugs at all. He was diagnosed with MS in 1990. After his third attack of optic neuritis in 1996, his neurologist recommended Copaxone. He didn’t have a warm relationship with his neurologist, and at first, the suggestion that he try a new drug made him feel wary.</div> <div> However, Joey Rowland is a high school biology teacher with a background in science; he began to read up on MS, and the evidence seemed pretty convincing. He soon began using Copaxone. He has never experienced any of the possible side effects, and has been taking Copaxone injections since 1997.</div> <div> Joey says his yoga practice, meditation, and attention to diet are just as important as his medication in helping him feel at ease with his illness. He does his injection in the morning, when he feels the least fatigued, and the shot is just one more of the daily routines he has developed to keep himself as healthy as possible—in body, mind, and spirit. Sometimes he does visualizations of his body being helped by the drug. He also sees it as a chance to practice his manual dexterity.</div> <div> Having a chronic disease that requires a daily injection has not stopped Joey Rowland from living his life to the fullest. He continues to teach, and he and his wife, Jexy, like to travel. Packing some Copaxone in the bag hasn’t been a hindrance.</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>Maggie Corcoran gets help</B></FONT></div> <div> Like Joey, Maggie Corcoran of Toronto, Ontario, was diagnosed with MS in 1990, before there were any approved treatments. She says she “moved along swimmingly” until 1993, when her MS started acting up, affecting her job as a production assistant at the Canadian Broadcasting Corporation. Her neurologist suggested that she try Rebif.</div> <div> “My husband said that we should go through this together. That was the tactic we took as a married couple and we’ve stuck with that. Everything we do with this disease, we do together,” she said.</div> <div> Maggie found that the injections were not the difficult part. Instead, the side effects were almost overwhelming. Since she had also started hormone therapy at the same time, it was hard to tell which side effects were due to which treatment. But she toughed it out, and stayed on Rebif, working with her doctor who tailored her dose to hold the side effects to a minimum. In time they diminished. Now she says she doesn’t have any reaction. “I might as well be injecting water,” she reports.</div> <div> Maggie thinks she may have had one small attack in the winter of 2002 when she and her family moved, but that is the first one since she started treatment in 1993. While she has quit her job and no longer plays tennis, “I’m still ambulatory and still driving,” she says. Overall, she feels confident that Rebif has slowed down her MS.</div> <div> <B>Which drug is best?</B></div> <div> This is a big question, complicated by competing claims in pharmaceutical company advertising. These claims are usually based on the design of a particular clinical trial and may mean relatively little when it comes to how a particular drug will affect an individual. There have been no large-scale definitive clinical trial comparisons among all four drugs, although Rebif received FDA approval by showing outcomes that were superior to Avonex in one trial.</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>Lifestyle questions</B></FONT></div> <div> The decision may come down to personal life-style matters such as timing, need for assistance, or need for refrigeration.</div> <div> Avonex requires a weekly injection into muscle; Betaseron, Rebif, and Copaxone require subcutaneous or under-the-skin injections, every other day for Betaseron, three times a week for Rebif, and daily for Copaxone. All four drugs are now available in pre-filled syringes, although Betaseron still requires mixing. Betaseron needs no refrigeration. Copaxone can be at room temperature for one week. Avonex must be refrigerated. Rebif can be kept at or below 77 degrees F, away from heat and light, for 30 days.</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>Side effects</B></FONT></div> <div> The interferons can produce flu-like symptoms, which are mild for some and major for others. People using Copaxone may have brief but intense episodes of chest discomfort, anxiety, and shortness of breath. Injection site reactions may occur with any injectable drug. They are less common with Avonex and may be more difficult to manage with Betaseron.</div> <div> Mimi experienced the flu-like chills and fever only once—after her very first Betaseron injection. Steve Paddison remembers the first three months when Avonex “slammed me hard.” The chills and fever are not bad now, but he still takes his shot on Friday night so he can use Saturday morning to recuperate if necessary. He also takes an over-the-counter pain killer to reduce the reaction. He may wake up on Saturday mornings feeling a little achy and groggy, but he says this wears off after he and his wife, Tiffany, go for a walk.</div> <div> Evelyn Pospisil of Long Island, New York, chose Copaxone because she didn’t want to risk the flu-like side-effects of the interferons. She felt that she could not afford to lose even a single day to feeling ill. She has experienced some injection-site redness and itchiness and says this has gradually become less of a problem.</div> <div> For most people, the interferon side effects lessen or disappear completely over time. Moreover, people figure out strategies to make the routine easier, just as Steve Paddison did. Taking an over-the-counter pain killer before injection is now recommended to everyone. In addition, physicians may start people on less than the full dose and increase it gradually to avoid these flu-like episodes.</div> <div> The excellent patient support programs run by each of the four pharmaceutical companies offer many coping tips from nurses, doctors, and from other people who are taking that drug. They also train people in safe injection techniques—which can go a long way toward preventing injection site problems.</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>Effective control of MS</B></FONT></div> <div> The choice of drug may hinge on your individual response. Do you continue to have many attacks over the course of a year? (A few attacks are expected.) Are the attacks accompanied by the appearance of neutralizing antibodies (or NAs) in the bloodstream? (It is not known what NAs really do, despite the word “neutralizing” in the name.)</div> <div> Your physician may be concerned about whether dosage levels are appropriate for your particular situation. Dosage levels differ among the four drugs. And for a minority of people, none of the disease modifiers work at all well. Then other options, and there are some, need to be explored.</div> <div> There is no consensus on these aspects of disease-modifying therapy at this time. The National MS Society urges all people with MS to consult a knowledgeable physician. Most insurance plans will cover second opinions if therapy is not working as expected.</div> <div> <B>Staying on course</B></div> <div> It is easier to start one of these drugs than it is to stay with it. It’s estimated that one third of the people who begin disease-modifying treatment stop after two years.</div> <div> People who stay with their treatment pinpoint two factors that help them keep going: knowledge and the feeling of control. “People with this disease must take charge of their lives, and taking one of these drugs is a good place to start,” Steve Paddison advised. Maggie Corcoran agreed: “You feel like you have to do something to gain some control over your life.”</div> <div> Despite his initial skepticism, Joey Rowland now believes that a disease-modifying drug is a good thing—and it doesn’t hurt to keep himself informed about new research.</div> <div> For Mimi Mosher, the treatment simply offers hope. She’s learned that hope goes a long way towards maintaining a positive attitude and a healthier body.</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>What’s the payoff?</B></FONT></div> <div> Why do people stop? Research shows that it is usually not the injections, annoying as they are. It isn’t the expense, although insurance problems are common. Sooner or later, a person on treatment may wonder about the payoff. The benefit of taking any one of these drugs may not be very obvious.</div> <div> Some people notice a reduction in their attacks but they may still have attacks. Existing symptoms tend to continue. In fact, there’s always the possibility that a new symptom will show up some morning. MRI images are interesting, but no one can feel the activity of the lesions pictured on them.</div> <div> As with so much else related to MS, this uncertainty is hard to live with. Some people throw up their hands and quit their treatment.</div> <div> <B>Separating “disease modification” from “symptom control”</B></div> <div> Evelyn Pospisil made her decision to begin treatment three months after her diagnosis in 1999. In addition to Copaxone, she has been given various other drugs to relieve the sometimes unbearable hypersensitivity in her hand, but without much success.</div> <div> Evelyn continues to work as an administrative assistant. She has found ways to type with just one hand. But during her first year on treatment, there were times when she felt so angry and frustrated that she skipped her injection.</div> <div> Finally, Evelyn accessed an MS chat board on the Web and asked how other people were dealing with symptoms that don’t disappear. She also checked out the newly diagnosed and “But You Look So Good” support groups affiliated with her National MS Society chapter. Realizing that other people with MS have had similar experiences and frustrations is helping Evelyn stay with her treatment.</div> <div> Maggie Corcoran keeps a journal to record her feelings, which she would recommend to anybody. She also goes once a month to a support group. “I was very leery of a support group,” she says. “Just because you have MS doesn’t mean you’re going to like all of the other people who have it.” But once she found the right group, she found friends, and, she says, “it does help.”</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>Marla Carson beats needle fear</B></FONT></div> <div> There have been many days when Marla Carson of Wisconsin has turned away from her Betaseron shot saying, “I don’t want to do this, I hate this.” But in the end she does it. Marla’s biggest hurdle has been her fear of injections.</div> <div> At first her husband gave her the shots. When her marriage ended, Marla wasn’t sure what to do. She still had needle-phobia, and worse, her hand tremors made it impossible for her to handle the syringe. Fortunately, an injection system with a hidden needle, the autoject2, became available for Betaseron. (Copaxone has a similar item available, the autoject and Rebif has the Rebiject hidden needle injector.) Marla can position the autoject2 and push the button herself.</div> <div> Marla often wishes disease-modifying drugs had been available in 1989 when she was first diagnosed. She didn’t have serious symptoms for the first five years but eventually had to stop working as a cashier and go on disability due to eye problems. Since then, she’s experienced tremors, bladder problems, and depression.</div> <div> Marla continues to work with her doctor on her bladder problems and finding the right antidepressant. But she’s glad that her disease has slowed down. Before Betaseron, she was having two or three MS attacks a year. After starting therapy, she had one attack a year and then went two years without one. Marla is confident that the disease-modifying drug is keeping her MS under control even though she still has many symptoms.</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>Being part of a work-in-progress</B></FONT></div> <div> Much of the evidence on the disease-modifying drugs is still relatively new. Not all doctors are going to agree on the best way to treat MS. Not all doctors will have the same level of experience with MS or with these medications. Some doctors might still advise their patients not to bother with treatment, or to wait until their symptoms are more severe before starting on an injectable therapy. Physicians who specialize in MS are far more confident, and this feeling is not lost on their patients.</div> <div> A study published in <B>Neurology</B> (October 12, 1999) reported that MS specialists were more likely than general neurologists to discuss the disease-modifying drugs with their patients. Of the people who began taking one, those who were seeing a neurologist who was not an MS specialist were more likely to quit.</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>When doubts build up</B></FONT></div> <div> People who are thinking about quitting should review all options first. Instead of keeping doubts bottled up, open the subject with health-care providers. Investigate ways that other people have handled similar problems.</div> <div> Practical issues, such as dealing with symptoms, side effects, injections, even insurance, usually have solutions. Instead of giving up, this might be the right moment to reevaluate personal strategies and incorporate some new coping tricks into your life.</div> <div> <B>A special issue: Pregnancy</B></div> <div> There was a time when women who had MS were routinely advised not to become pregnant. Present evidence shows that pregnancy has no long-term adverse effects on women who have MS. Couples who are thinking about having a child should consider how they will manage symptoms or disabilities after the baby is born—and later when the baby becomes an active older child. The couple should speak with their doctors about all the medications they might be taking, including Avonex, Betaseron, Rebif, Copaxone, or Novantrone.</div> <div> In the absence of convincing evidence to the contrary, physicians tell women to stop the disease-modifying drugs before conception and not to resume until after the end of breastfeeding. Birth control is essential for women or men taking Novantrone. Sperm or egg banking before Novantrone treatment starts is also recommended, just as it is for many other chemotherapeutic and cytotoxic drugs.</div> <div> MS has no effect on the ability to conceive or to have a successful pregnancy. Pregnancy does have an effect on MS. Women tend to have fewer or no attacks during the last trimester. New mothers are at higher than normal risk of an MS attack in the first six months following delivery. This see-saw effect balances out. There are no long-term effects of pregnancy on the course of MS.</div> <div> However, adjusting to motherhood and having an MS attack at the same time is a heavy burden. Many women resume taking their disease-modifying drug immediately after delivery, in hope of forestalling this. If they do, they are advised to forego breastfeeding. There are no clinical trial data on the safety of these drugs for nursing infants.</div> <div> <B>The money matters</B></div> <div> Avonex, Betaseron, Rebif, and Copaxone are expensive drugs, usually self-administered, at home, which affects reimbursement policy. Novantrone, delivered by a physician in a health-care facility does not pose the same sort of insurance coverage problem.</div> <div> For many people who decide to begin treatment, getting approved by their insurance company is a major hurdle. Insurers who cap annual drug costs at $1,500 or require a 20% co-pay for injectable drugs place a formidable burden on family finances. People without insurance that covers prescription drugs, such as Medicare, for example, face more problems.</div> <div> The four drug manufacturers offer knowledgeable insurance advice and limited financial support programs. The National MS Society brochure <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Comparing the Disease-Modifying Drugs</U></FONT> outlines what each one offers.</div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="339" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 39 WIDTH="113"><div> <B>Drug</B></div> </tD> <tD VALIGN=TOP WIDTH="219"><div> <B>Patient Support/Phone Number</B></div> </tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 56 WIDTH="113"><div> <B>Avonex</B></div> </tD> <tD VALIGN=TOP><NOBR><div> MS Active Source</div> <div> 800-456-2255</div> <div> <U>www.msactivesource.com</U></div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 56 WIDTH="113"><div> <B>Betaseron</B></div> </tD> <tD VALIGN=TOP WIDTH="219"><div> MS Pathways</div> <div> 800-788-1467</div> <div> <U>www.mspathways.com</U></div> </tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 56 WIDTH="113"><div> <B>Rebif</B></div> </tD> <tD VALIGN=TOP WIDTH="219"><div> MS LifeLines</div> <div> 877-44-REBIF</div> <div> <U>www.mslifelines.com</U></div> </tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 75 WIDTH="113"><div> <B>Copaxone</B></div> </tD> <tD VALIGN=TOP><NOBR><div> Shared Solutions</div> <div> 800-887-8100</div> <div> 800-283-0034 Canada</div> <div> <U>www.sharedsolutions.com</U></div> </NOBR></tD> </tR> </TABLE></div> <div> <B>PART II: BACKGROUND ON MS AND TREATMENT</B></div> <div> People experience the symptoms of MS-blurred vision, spasticity, weakness, fatigue, gait problems, difficulty with memory and concentration, and the like—after myelin in the central nervous system is damaged. Myelin, the protective fatty sheath that wraps the nerve fibers and serves as an insulating material, is attacked by the body’s immune system in MS. Scars, or plaques, eventually result. They interfere with the normal transmission of nerve signals. This, in turn, causes the body to malfunction. MS may also break or damage the underlying nerve fiber, or axon. Eventually, accumulated axonal damage results in loss of brain tissue or atrophy. This tissue damage is associated with long-term disability.</div> <div> The immune system functions by identifying foreign substances and marking them for destruction. Specialized white blood cells then launch an attack to destroy these substances. This job is done with the help of a complex array of molecules produced by specialized groups of immune-system cells. In MS, the immune system incorrectly identifies and damages the body’s own myelin and the nerve fibers.</div> <div> MS has been treated with <B>immune-suppressing</B> drugs such as <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>azathioprine, cyclophosphamide, and methotrexate</U></FONT>—with some benefit. These drugs may also make people susceptible to other diseases since immune system activity is widely suppressed. The newer disease-modifying drugs are <B>immunomodulators</B>: They are able to intervene in or modulate specific immune processes. They do not suppress the entire system.</div> <div> The beta interferons, marketed as Avonex, Betaseron, and Rebif, are forms of a natural immune protein normally present in the human body. Glatiramer acetate, marketed as Copaxone, is composed of four synthetic amino acids. While scientists still don’t know exactly how any of these agents act, the beta interferons appear to suppress or “down-regulate” the activity of a specific group of immune system cells. Copaxone may modulate immune responses by acting as a decoy and binding some molecules that would otherwise bind to myelin and trigger destruction. Or Copaxone may stimulate certain white blood cells to suppress the release of attacking molecules.</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>New understandings about MS</B></FONT></div> <div> Scientific understanding of MS was originally based only on observation of people with the disease or information learned from autopsies. MRI technology was applied to MS in the early 1980s. It allowed researchers to see the course of the disease inside the living brain for the first time. MRI can “picture” the white matter in the brain and spinal cord, including areas of active inflammation and myelin loss.</div> <div> Sequential, or serial MRI studies proved that MS is active, with new lesions forming, during periods of remission when the person has no or few active symptoms. This activity is especially pronounced early in the disease.</div> <div> However, lesions can form without immediately affecting the individual’s abilities or function. There is still no clear-cut correlation between disease activity as seen on MRI and the onset of an attack or the worsening of specific symptoms, although the two are linked.</div> <div> In the early stages of MS, the central nervous system may be replacing lost myelin or compensating for myelin damage by using alternative nerve pathways. But as the disease continues, damage to the underlying axons or nerve fibers and an increasing burden of lesions in the brain appears to overwhelm these recovery mechanisms, setting the stage for significant disability and losses of function.</div> <div> ·<FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT><FONT SIZE="3" COLOR="#660099" FACE="Arial" ><B>The bottom line</B></FONT></div> <div> MRI studies of the natural history of MS, which looked at the course of untreated MS, have shown that, on average, a person has five brain lesions at the time of diagnosis. Without treatments, the person will develop from three to five additional lesions every year. The disease-modifying drugs reduce this by 40 percent. Novantrone’s effect is even more dramatic.</div> <div> Dr. Donald W. Paty, of the Division of Neurology at the University of British Columbia and the Vancouver Hospital & Health Sciences, has over thirty years of experience treating people with MS. He has seen the effect the disease-modifying drugs have on slowing the progression of the disease. He says, “I’d give them to almost everybody with MS. They are not dangerous drugs and the side effect profile is fine for long-term use.”</div> <div> These drugs are the best option science currently has. More effective drugs, less difficult to take, are surely in the research pipeline. But time is not on the side of the person who has MS right now.</div> <div> While the research continues, the National MS Society strives to help people find the options they need now, including access to health-care professionals with MS experience. The Society invites participation in its programs to advocate for better prescription drug insurance plans and for equity in Medicare coverage. And it offers thousands of affiliated self-help groups and peer counseling programs where people with MS can learn from each other. These are just a phone call away.</div> <div> <B>PART III: REFERENCES</B></div> <div> <FONT SIZE="3" COLOR="#660099" FACE="Symbol" >·</FONT><FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT>Holland, Nancy J., Murray, T. Jock and Reingold, Stephen C., <B>Multiple Sclerosis: A Guide for the Newly Diagnosed</B>, 2nd Edition, New York: Demos Medical Publishing (386 Park Avenue South, Suite 201, 10016), 2002. 160 p. $21.95 ISBN 1-888799-60-9. <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>www.demosmedpub.com</U></FONT></div> <div> A book for people who have just been diagnosed, their families and friends, it provides a guide to the disease, its potential impact, and current medical treatments.</div> <div> <FONT SIZE="3" COLOR="#660099" FACE="Symbol" >·</FONT><FONT SIZE="1" COLOR="#660099" FACE="Arial" > </FONT>Kalb, Rosalind C., <B>Multiple Sclerosis: The Questions You Have—The Answers You Need</B>, 2nd Edition, New York: Demos Medical Publishing (386 Park Avenue South, Suite 201, 10016), 2000. 626 p. $39.95 ISBN 1-888799-43-9. <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>www.demosmedpub.com</U></FONT></div> <div> The title says it all; a voluminous reference guide.</div> <div> The Consensus Statement was developed in 1998 by the MS Disease Management Advisory Task Force, comprised of a panel of experts from the following organizations: National Multiple Sclerosis Society, Consortium of MS Centers, American Academy of Neurology, Paralyzed Veterans of America (consultants).</div> <div> It was updated by the Executive Committee of the National MS Society’s Medical Advisory Board in October, 2002.</div> <div> <B>For additional information</B></div> <bR> <div> <I>Lorna Smedman is a freelance health writer and former managing editor of the Society’s magazine, </I>InsideMS<I>.</I></div> <div> <I>Cover photograph: A self-help group at the Northern California Chapter of the National MS Society. Photograph by Edward Caldwell.</I></div> <div> <I>This publication is supported by contributions to the National Multiple Sclerosis Society from its members and friends.</I></div> <div> <I>Reviewed by members of the Client Education Committee of the National Multiple Sclerosis Society’s Medical Advisory Board.</I></div> <div> Copyright © National Multiple Sclerosis Society, 2004</div> <bR> <bR> <div> <B><U> <A NAME="fda_approves_new_drug_for_treating__ms_"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>FDA approves new drug for treating  MS  12/14/2004  </U></B></div> <div> <B>  natalizumab, which will be marketed as Tysabri, </B></div> <div> <B>The drug for multiple sclerosis uses a humanized monoclonal antibody to prevent immune cells from reaching the brain and spinal cord.</B></div> <bR> <div> <B>By Susan J. Landers, AMNews staff. Dec. 20, 2004.</B></div> <bR> <div> <B>Washington -- The Food and Drug Administration has licensed a new medication to treat the flare-ups of multiple sclerosis that occur in the majority of the 400,000 patients diagnosed with this chronic disease of the brain and spinal cord.</B></div> <bR> <div> <B>The drug, natalizumab, which will be marketed as Tysabri, was granted accelerated approval based on promising first-year results from a two-year trial now concluded. Its data are being analyzed.</B></div> <div> <B> With this article</B></div> <div> <B> * Links</B></div> <div> <B> * See related content</B></div> <bR> <div> <B>But until the final results are in, physicians who specialize in treating patients with multiple sclerosis are eyeing the new offering with cautious optimism.</B></div> <bR> <div> <B>"I'm excited about what I consider to be this preliminary data," said Jack Burks, MD, a Reno, Nev., neurologist who specializes in treating patients with multiple sclerosis. "But I am waiting until the first quarter of next year when I can get the two-year data to see if my excitement is sustained or not. We've had the experience with drugs that have better one-year data than two-year data."</B></div> <bR> <div> <B>However, his patients are already clamoring for Tysabri, which many think may represent a cure.</B></div> <bR> <div> <B>"I would not take anyone who is doing well off their medication. If it ain't broke we don't need to fix it," said Dr. Burks, who is also the vice president and chief medical officer of the Multiple Sclerosis Assn. of America.</B></div> <bR> <div> <B>"The clinical trial results indicate that the drug is very effective in relapsing forms of MS and appears to be well-tolerated," said Aaron Miller, MD, chief medical officer of the National Multiple Sclerosis Society. The relapsing-remitting form of MS is the most common form of the disease and is characterized by symptoms that become dramatically worse before subsiding totally or partially.</B></div> <bR> <div> <B>Dr. Miller also recommends close monitoring of the drug for any potential safety problems as it becomes more widely used.</B></div> <div> <B>How it works</B></div> <bR> <div> <B>The new drug, which is administered by intravenous infusions every four weeks, is the sixth drug now approved for the long-term treatment of MS and the first humanized monoclonal antibody available to treat the disease.</B></div> <bR> <div> <B>"We believe Tysabri will revolutionize the treatment of MS and become the leading choice for patients and physicians," said James C. Mullen, chief executive officer of Biogen Idec Inc., which manufactures the drug with Elan Corp.</B></div> <div> <B>400,000 Americans have multiple sclerosis.</B></div> <bR> <div> <B>"Tysabri is a significant breakthrough for patients with MS," said Kelly Martin, president and chief executive officer of Elan.</B></div> <bR> <div> <B>Tysabri is designed to interfere with movement of potentially damaging immune cells from the bloodstream across the blood-brain barrier and into the brain and spinal cord. Although the cause of MS remains unknown, it is widely considered to be an autoimmune disease.</B></div> <bR> <div> <B>Tysabri apparently blocks the immune cells' movement by attaching to alpha 4-integrin, a protein on the surface of immune T cells that normally enables the cells to pass through the blood-brain barrier.</B></div> <bR> <div> <B>The one-year data for Tysabri showed a 66% reduction in relapses compared with patients on placebo in one trial and a 54% relative reduction in relapses for those taking Tysabri in combination with a second drug approved to treat MS -- Avonex, or interferon beta-1a -- as compared with those taking Avonex alone.</B></div> <bR> <div> <B>Common side effects include headache, fatigue, urinary tract infection, depression, lower respiratory tract infection, joint pain and abdominal discomfort.</B></div> <bR> <bR> <bR> <div> <U> <A NAME="new_test_for_ms"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U><U>New Test for MS</U></div> <bR> <div> NEW YORK (Reuters Health) - A protein pattern or "molecular footprint" in the blood can distinguish patients with multiple sclerosis from healthy subjects, preliminary research suggests, which could make diagnosis of the disease much easier.</div> <div>      </div> <bR> <div> Dr. Gary M. Wolfe, at Predictive Diagnostics in Vacaville, California, and colleagues obtained blood samples from 25 patients with newly diagnosed multiple sclerosis and 25 healthy subjects. A special X-ray test and computer software were used to identify protein patterns associated with the neurologic disorder.</div> <bR> <div> According to the report in the Journal of Molecular Neuroscience, the test identified three patterns seen only in patients with multiple sclerosis, not in healthy subjects.</div> <bR> <div> When multiple sclerosis is suspected in a patient, even the combination of brain scans, analysis of spinal fluid and patient history may not be sufficient to provide a clear diagnosis, Wolfe told Reuters Health.</div> <bR> <div> Therefore, "the idea of using a simple blood test for diagnosing multiple sclerosis is huge news," he said.</div> <bR> <div> Previously, Wolfe's team applied the same techniques to identify protein patterns associated with Alzheimer's disease and certain cancers.</div> <bR> <div> SOURCE: Journal of Molecular Neuroscience, February 2005. </div> <bR> <bR> <div>  <A NAME="copaxone_"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A>Copaxone (<FONT SIZE="3" COLOR="#660099" FACE="Arial" >Glatiramer Acetate Injection) May Protect Against Axonal Injury Over the Long-Term in Relapsing-Remitting Multiple Sclerosis</FONT></div> <div>  "Copaxone (Glatiramer Acetate Injection) May Protect Against Axonal Injury Over the Long-Term in Relapsing-Remitting Multiple Sclerosis"</div> <bR> <bR> <div> Additional Long-Term Efficacy in Both Clinical and MRI Parameters Also Highlighted At European Neurological Society Meeting KANSAS CITY, MO -- June 30, 2005 -- New data presented at the European Neurological Society Meeting (ENS) demonstrated key clinical and magnetic resonance imaging (MRI) effects of Copaxone(R) (glatiramer acetate injection) in the treatment of relapsing-remitting multiple sclerosis (RRMS). Results highlighted sustained beneficial effects on cerebral axonal injury and the value of starting Copaxone treatment early to slow the accumulation of long-term disability as measured by the Expanded Disability Status Scale (EDSS). MRS results suggest beneficial effect of Copaxone on cerebral axonal injury Brain n-acetylaspartate (NAA) levels, a marker of neuronal integrity and function, are measured by magnetic resonance spectroscopy (MRS). An increase in brain NAA levels relative to creatinine (NAA/Cr ratios) indicates a recovery of injured nerve cells or neurons in the brain. Preventing or minimizing damage to nerve cells is critical in reducing long-term disability in multiple sclerosis. The open-label study involved 18 RRMS patients (15 of whom were followed for three years). Assessments included EDSS scores and annual MRI/MRS scans. Additionally, four untreated controls were followed for the first two years. Two of these patients began therapy with Copaxone(R) for the third year of the study. The data were presented by Omar Khan, M.D., associate professor of neurology and director of experimental therapeutics/clinical research, Multiple Sclerosis Center, Wayne State University. Unlike the gadolinium-enhanced MRI, increases in NAA levels as measured by MRS, may indicate reversal of axonal loss, which strongly correlates to improved clinical disability. Dr. Khan commented on the results, "Copaxone(R) treatment led to increased NAA/Cr ratios, suggesting improved cerebral axonal recovery in RRMS patients, indicating a potential benefit on the pathways of electrical conduction in the brain." Copaxone (glatiramer acetate injection) sustained this improvement over a three-year period, compared to pretreatment baseline and untreated controls. Further, in two of the four untreated control patients who began Copaxone(R) treatment after two years of no treatment, an increase in NAA concentrations was observed during the third year of the study, compared to the continued decline observed in the two patients who remained untreated. "These MRS data suggest an action of Copaxone in the central nervous system (CNS), resulting in a sustained beneficial effect on cerebral axonal injury. No other approved treatment for RRMS has been shown to have a beneficial effect on MRS scans over a three-year period. This study also supports the emerging concept of Copaxone as a neuroprotective agent in addition to helping reduce relapses. Additional research investigating the potential neuroprotective attributes of Copaxone is ongoing," explained Dr. Khan. Early intervention with Copaxone(R) slows the accumulation of long-term disability Marco Rovaris, MD, Neuroimaging Research Unit, Department of Neuroscience, Scientific Institute and University of Ospedale San Raffaele, Milan, presented long-term, open-label data (at almost six years) in patients who had originally participated in a blinded MRI study which demonstrated the efficacy of Copaxone. Two hundred and twenty-four patients entered the nine-month placebo- controlled study. Of these, 142 entered an open-label extension in which all patients were treated with Copaxone. Patients continued to be assessed for an average of 5.8 years. Patient visits involved clinical assessments and included EDSS scoring. A higher proportion of patients who were continuously on Copaxone(R) (glatiramer acetate injection) (n=73) did not reach significant disability as defined by EDSS scores equal to or greater than six compared to those who were on placebo for the first nine months, then switched to Copaxone (n=69, P =.03). Significant disability in the analysis was the point at which patients require intermittent or unilateral (one-sided) constant assistance, such as a cane, crutch, or brace. These results suggest early initiation of Copaxone in patients with active RRMS may have a positive impact on long- term disease evolution by slowing the progression to significant disability. About Copaxone Current data suggest Copaxone is a selective MHC class II modulator. Copaxone is indicated for the reduction of the frequency of relapses in relapsing-remitting multiple sclerosis. The most common side effects of Copaxone are redness, pain, swelling, itching, or a lump at the site of injection, weakness, infection, pain, nausea, joint pain, anxiety, and muscle stiffness. Copaxone is now approved in 44 countries worldwide, including the United States, Canada, Mexico, Australia, Israel, and all the European countries. In Europe, Copaxone is marketed by Teva Pharmaceutical Industries Ltd. and sanofi-aventis. In North America, Copaxone is marketed by Teva Neuroscience. SOURCE: Teva Neuroscience</div> <bR> <div>  <A NAME="not_all_interferon_beta_treatments_are"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A>Not all Interferon-beta Treatments are Created Equal </div> <div> in Developing Neutralizing Antibodies</div> <bR> <div> Neutralizing Antibodies can significantly decrease the effectiveness of IFN-b in the treatment of MS</div> <bR> <div> TORONTO, ONTARIO -- July 14, 2005 -- Three studies published in Neurology which included more than 1200 patients, confirm that the three interferon preparations used to treat relapsing-remitting multiple sclerosis (MS) vary in their rate of production of neutralizing antibodies (NAbs).</div> <bR> <div> Further, there is agreement that NAbs reduce or eliminate the biologic activity and clinical efficacy of the interferon-beta (IFN-b) therapies.</div> <bR> <div> Once-weekly Avonex® (interferon beta-1a IM) was shown to be significantly less likely to induce the development of NAbs than the other two available interferon therapies (Rebif® and Betaseron®). Since NAbs reduce or eliminate the clinical benefits of the interferons, these studies highlight a concern for MS patients, neurologists and those who pay for these medications.</div> <bR> <div> For the many Canadians living with MS, and currently being treated with IFN-b therapy, this is important data.</div> <bR> <div> "MS is a chronic disease, and patients need to have the confidence that their therapy will retain its efficacy throughout the course of treatment, which is often for many years," commented Dr. Stanley Hashimoto, neurologist and former medical director of the University of British Columbia MS Clinic, Vancouver, Clinical Director of the UBC MS Clinic, Vancouver, British Columbia. "These studies confirm that in MS, high titre and persistent NAbs are very important in eliminating the efficacy of the therapeutic agent. It is important that we have available a less immunogenic option such as Avonex®."</div> <bR> <div> While each of the studies showed slightly different rates of NAbs, Avonex® (interferon beta-1a IM) consistently demonstrated the lowest rates as compared to the other IFNb therapies. For example, in the first study the Danish Multiple Sclerosis Study group (Neurology 2005;65:33-39) concluded, "Unlike previous findings reported in the literature we did not find any difference in the proportion of patients treated with [Betaseron®] and [Rebif®] who became NAb-positive, but could confirm that Avonex® is much less immunogenic."</div> <bR> <div> In the second study, Kappos and associates (Neurology 2005;65:40-47) analyzed 395 patients over four years in a controlled trial, and clearly demonstrated the loss of efficacy in terms of relapse rate reduction and disability progression over a significant number of years. It can be assumed from this research, that persisting NAbs beyond the four years will continue to suppress the therapeutic activity of the interferons. This was also echoed by Drs. Giovannoni and Goodman in their Editorial (Neurology 2005;65:6-8).</div> <bR> <div> The third study, authored by Dr. Gordon Francis et al. (Neurology 2005;65:48-55), concluded that, "Neutralizing antibody development in IFN-b-treated patients is correlated with reduced efficacy and is a potential cause for renewed (MS) disease activity."</div> <bR> <div> "Many patients being treated for MS are not getting the efficacy they deserve because of the neutralizing effect of NAbs," said Dr. Hashimoto "This is not to mention the fact that our healthcare system is paying for these drugs without realizing the potential negative effects of neutralizing antibodies."</div> <bR> <div> The Danish Multiple Sclerosis study group agreed that the presence of NAbs decrease or eliminate efficacy of the interferons. They recommended that to avoid these negative consequences, all patients on the therapies should be tested at six-month intervals for two years when it becomes less likely the new positivity will develop. Routine testing will assure patients that they are self-injecting their medication and getting benefit from it.</div> <bR> <div> With recent concerns about existing and future MS treatments, patients and physicians are reassessing currently available therapies, like the interferons. As a result, it is more important than ever to re-evaluate which therapy will provide efficacy over the long-term, including minimizing the formation of NAbs.</div> <bR> <div> Multiple sclerosis is the most common neurological condition affecting young adults in Canada. MS most often strikes young adults -- women and men between 20 and 40 who are in their most productive family and career years. Women are affected twice as often as men.</div> <bR> <bR> <div> Avonex® is a registered trademark of Biogen Idec Inc.</div> <div> Rebif® is a registered trademark of Serono Canada Inc.</div> <div> Betaseron® is a registered trademark of Berlex Canada Inc.</div> <bR> <bR> <div> SOURCE: Biogen Idec Inc. </div> <bR> <bR> <div>  <A NAME="vitamin_b12_demyelination"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A>Vitamin B12, demyelination, remyelination and repair in multiple sclerosis.</div> <bR> <div> Miller A, Korem M, Almog R, Galboiz Y.</div> <bR> <div> Division of Neuroimmunology and Multiple Sclerosis Center, Carmel Medical Center, Haifa 34362, Israel. millera@tx.technion.ac.il</div> <bR> <div> Multiple Sclerosis (MS) and vitamin B12 deficiency share common inflammatory and neurodegenerative pathophysiological characteristics. Due to similarities in the clinical presentations and MRI findings, the differential diagnosis between vitamin B12 deficiency and MS may be difficult. Additionally, low or decreased levels of vitamin B12 have been demonstrated in MS patients. Moreover, recent studies suggest that vitamin B12, in addition to its known role as a co-factor in myelin formation, has important immunomodulatory and neurotrophic effects. These observations raise the questions of possible causal relationship between the two disorders, and suggest further studies of the need to close monitoring of vitamin B12 levels as well as the potential requirement for supplementation of vitamin B12 alone or in combination with the immunotherapies for MS patients.</div> <bR> <div> PMID: 15896807 [PubMed - in process]</div> <bR> <bR> <bR> <div>  <A NAME="mitoxantrone_effective_and_well"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><FONT SIZE="4" COLOR="#660099" FACE="Arial" >Mitoxantrone Effective and Well Tolerated for Treatment of Multiple Sclerosis in Daily Clinical Practice</FONT>: Presented at ENS</div> <div>  "Mitoxantrone Effective and Well Tolerated for Treatment of Multiple Sclerosis in Daily Clinical Practice: Presented at ENS"</div> <bR> <bR> <div> VIENNA, AUSTRIA -- June 24, 2005 -- Patients with multiple sclerosis (MS) who have taken mitoxantrone (Novatrone, Onkatrone) for 2 years or more tolerate therapy well and delay disease progression, according to investigators who presented findings here June 20[th at the 15th meeting of the European Neurological Society (ENS).</div> <bR> <div> Principal investigator Isabel Boscà Blasco, MD, Consultant Neurologist, Hospital Universitari La Fe, Valencia, Spain, said during the presentation that the study dose was initially 10 mg/m2 and titrated upward to a maximum of 120 mg/m2.</div> <bR> <div> Dr. Boscà Blasco and co-investigators conducted their study to evaluate MS patients' response and tolerability mitoxantrone in a clinical practice setting. They followed 49 women and 22 men, who were an average of 42.7 years old, and had MS for an average of 14.6 years.</div> <bR> <div> Baseline Expanded Disability Status Scale (EDSS) was an average of 5.7, and patients sustained an average EDSS decrease of more than 1.0 in the year before treatment began. Their annual relapse rate in the previous year was an average of 0.9, and all had been treated previously with interferon.</div> <bR> <div> Patients were followed prospectively for at least 1 year, with a follow-up range of 12 to 36 months. The initial dose was a 10 mg/m2 injection every 3 months, titrated upward until patients were either taking a maximum dose of 120 mg/m2 or had stopped treatment due to lack of efficacy or adverse effects.</div> <bR> <div> All patients underwent a ventriculography before treatment and every six months, and before each infusion, they submitted a blood sample for analysis prior to each infusion. The investigators calculated the EDSS, number of relapses, and the Functional Composite MS scales at every three-month visit, as well as adverse effects.</div> <bR> <div> The researchers have followed 22 patients for 2 years and 14 patients for 3 years. In the group of patient followed for 2 years, the annual relapse rate decreased by 82%, with 77.3% of patients relapse-free. The EDSS increased by 0.18 points.</div> <bR> <div> In the whole cohort, 19 patients had withdrawn from treatment, seven for lack of efficacy, nine due to adverse effects, one due to relocation, and two at the patients' request.</div> <bR> <div> The remaining 16 patients have not yet been followed for 2 years.</div> <bR> <div> Among the nine patients who withdrew due to adverse events, seven had a decrease in the left ventricular ejection fraction (LVEF) of more than 10% or below the study's 50% threshold. One patient had symptoms of cardiac failure.</div> <bR> <div> Adverse events recorded among the 71 patients were mild in 68 cases, moderate in 17 and serious in three. Rates of adverse events were 30.9% for nausea and vomiting, 20.3% fatigue, 9.8% infection, 9.8% alopecia, 33.8% leucopenia, 16.3% amenorrhea, and cutaneous necrosis and cardiac insufficiency 1.4%.</div> <bR> <div> The investigators concluded that mitoxantrone, when given at this dosing schedule, was safe and well tolerated, helped prevent relapses and slowed disease progression, Dr. Boscà said.</div> <bR> <bR> <div> [Presentation title: Mitoxantrone Therapy in Multiple Sclerosis. Safety and Efficacy in Daily Clinical Practice. Abstract P230]</div> <bR> <bR> <bR> <bR> </td> </tr></table></body>