Are common viral infections risk factors for pediatric MS?Emmanuelle Waubant, M.D., Ph.D.

Multiple studies have shown that Epstein-Barr virus (the “kiss virus” responsible for mononucleosis) increases the risk of MS both in adults and children throughout the world. The center at UCSF has led a collaborative study with the other centers of the US Pediatric MS Network sponsored by the National MS Society to evaluate the role of other common viruses typically acquired during childhood. Our group has found that past infection with cytomegalovirus may decrease by four times the risk to develop pediatric MS. In addition, a past infection with herpes simplex virus type 1 also decreases the risk of pediatric MS only in people with a specific gene. In contrast, a past infection with herpes simplex virus type 1 in people who do not have

this gene increase pediatric MS risk by a factor of four. These intriguing findings will be further studied in a large North American study in children. This study sponsored by a grant from the National Institute of Health will also investigate a wide range of factors in the environment during pregnancy and the first years of life as possible risks factors for pediatric multiple sclerosis. This study will enroll both patients with recently diagnosed pediatric MS and matched controls for a single visit at 10 pediatric MS centers in the USA. To know more about this study or to refer participants, please email janace.hart@ucsf.edu or call 415-514-2476.

University of California, San Francisco

Regional Pediatric Multiple Sclerosis Center

Spring 2011 News Brief

1

Update on treatment of severe and refractory MS in the pediatric age groupJonathan Strober, M.D.

As more children are being diagnosed with multiple scle-rosis, it is important to know that the medications we pre-scribe are at least as safe and effective as in adults. A re-cent study on the treatment of 258 patients with refractory pediatric MS, found that 56% of children only needed one therapy while 25% required a change in therapy once and only 8% of patients required three or four therapies over a period of four years. Of those children changing medi-cation 37% were changed due to poor tolerance or non-compliance while the rest were changed due to refractory disease. There was no difference in tolerability or compli-ance amongst all three of the different interferons (Avonex, Betaseron and Rebif) and no difference in the group being treated with glatiramer acetate (Copaxone) compared to the interferon group for tolerability, compliance or break-through disease. Interestingly, Hispanic children were more likely to require a change, with 50% of these chil-

dren requiring a change due to breakthrough disease ver-sus only 24% in the non-Hispanic group. Of those children going on to a second therapy due to refractory disease 58% responded to treatment with the second agent. Of those switching due to poor tolerability or noncompliance almost 1/3 changed therapy again due to the same reason. Overall, the rate of refractory disease in patients treated with first-line therapy seems to be similar for children and adults (approximately 30%).

Clinicians have also been increasing the use of natali-zumab in children. The biggest concern with its use is the possible development of progressive multifocal leukoen-cephalopathy (PML), estimated to occur in one per 1,000 treated adults. An open-labeled study of this drug to evalu-ate its safety and efficacy in Italian MS patients under the age of 18 years was published this past year. The patients

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Parents’ Frequently Asked QuestionsLaura Julian, Ph.D. and Jason Rosenbury, MSW

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Our adolescent is finishing high school and wants to go away to college. Is this OK?

When the time comes for college, there are many factors to consider. Whether someone has MS or not, going away to college is a big decision not to be taken lightly. Overall, we do not discourage teens from going away to college. However, it is appropri-ate to consider several factors in this decision including: your adolescent’s maturity, relevant study program or school of his/her interest, availability of additional supports if needed (both academically and psychosocially), and availability of medical care and the development of medication plans. Depending on your child’s status, staying closer to home or starting with a junior college may be another choice to consider. For more information about college related and post high school information, a resource developed by National MS Society, Moving Forward: A Guide to College and other Life Choices for Teens with MS, will be available in print this year.

I have heard of Section 504 and something called an IEP, what are these? How can they help my child?

Section 504 is a civil rights law; it protects any individual with a disability (students, parents, teachers, guests, and the public). Under Section 504, an individual with a disability is any individual who:

• Hasaphysicalormentalimpairment,whichsubstantiallylimitsoneormoremajorlifeactivities,• Hasarecordofsuchanimpairment,• Isregardedashavingsuchanimpairment.

IndividualizedEducationProgram(IEP) istheproductof IndividualswithDisabilitiesEducationAct(IDEA),which isafederallaw.Itrequiresschooldistrictstoprovidespecialeducationandrelatedservicestoeligiblechildrenwithdisabilities.Afterthestudentisassessedandfoundtobeeligible,anindividualizededucationalplan(IEP),designedforeachchild’suniqueneeds,isdevelopedbyschoolstaffandisreviewedatascheduledIEPmeeting,whichrequiresparentattendance.ToqualifyforservicesunderIDEA,achildmustfallintooneofseveralcategories(13)thatcanincludephysical,cognitiveandemotionalimpairment.

AchildcanbeeligibleunderIDEAandmeettheSection504definitionofdisability.Section504alsoprotectsthosechildrenwhoarenoteligibleforIDEAservices.Forexample,achildwithMSwhodoesnotneedspecialeducation(becauseheorsheisnot having academic or behavioral problems) is still covered by Section 504 if s/he needs aids and/or services within the regular educational setting. For more information on accommodations/services at school, please refer to the Handbook for Parents with Children with Pediatric MS. Foracopyofthisbook,calltheUCSFPediatricMSCenterat415-353-3939.

Should I limit my child’s exposure to stress? Can my child still participate in sports? Should I keep them out of other potentially stressful activities (e.g., extracurricular, sports, drama club, dating)?

Dealing with stress is an inevitable, normal part of human development and life in general for all people, whether they have MS ornot.Itismorerealistictosupportyourchildthroughwhateverstresstheymayfacethantotrytoavoidit.Youranxietyaboutyourchild’sstresslevelsandhealthingeneraliscommon,naturalandunderstandable.Asfarashavingyourchildparticipatein activities, one of our main goals is to try to help patients have as “normal” a life as possible. Keeping them out of activities will only serve to make your child angry at these unnecessary limitations that you set, and angry at the people who are setting them(you!).Theonlyreasontokeepachildoutofactivitiesiswhenthoseactivitiesareclearlyunsafe.Experiencingallthedif-ferent activities you listed will actually help your child to mature and develop social and interpersonal skills, including managing (not avoiding) stress.

The Pediatric MS Teammanaging stress at work

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The accepted notion that MS is more common in white adults compared to other racial categories is challenged by recent findings in the database of Kaiser Permanente Southern California by Annette Langer-Gould, M.D., Ph.D. and colleagues. The Kaiser database is representative of the general population, and thus can be used to determine the number of new cases of specific disorders in the gen-eral population. One study in Canada recently reported that the number of new cases of first time inflammation in the brain and spinal cord in children was approximately 0.9 per 100,000 children every year. The study included patients with MS, acute demyelinating encephalomyelitis, neuromy-elitis optica, optic neuritis, and complete transverse myeli-tis, but did not investigate the number of new cases by race or ethnicity. This new study by Langer-Gould et al. shows that the estimated number of new cases of first time inflam-

mation of the brain and spinal cord is approximately 1.6 per 100,000 individuals, which is overall similar to the Canadian study. The novel finding is that African American and Asian children are twice as likely as whites to develop pediatric MS. Similarly, African American and Asian children are also more likely to develop other types of inflammation of the brain and spinal cord than whites. These findings suggest that MS risk in the US is in fact lower in white children com-pared with other racial groups. It is important to confirm these findings in the adult Kaiser database in order to de-termine whether this racial difference is specific to children or whether it is also reported in adults. According to this new study, the number of new pediatric MS cases in the US might be at least 0.51 per 100,000 individuals every year (i.e. 380 new pediatric MS cases per year).

The annual number of new pediatric MS cases is higher in African American and Asian children compared to whitesEmmanuelle Waubant, M.D., Ph.D.

had to have either two or more relapses, or a severe re-lapse with incomplete recovery, in the two years prior while on interferon or glatiramer acetate treatment or at least two relapses in the previous year with new gadolinium-enhanc-ing lesions on MRI without any prior treatment. Nineteen patients were treated. There were no relapses in all pa-tients treated. One patient had transient worsening of pre-vious symptoms immediately after the first infusion. Only 10 adverse events were reported; three patients developed transient headache, two vertigo and one patient each had pharyngitis, itching, nausea, diarrhea and fatigue.

Overall, this study showed that natalizumab appears to be safe in pediatric MS. One note of caution, the median treatment duration to onset of symptoms of PML was 25

months in adult cases, however the longest treatment du-ration in the above study was 25 months and this was only for two patients. Therefore, these patients will need to be followed for longer periods on treatment before we have a better idea of the true safety of this drug in this age group. Hopefully, the recent ability to test our patients for expo-sure to JC virus, the reactivation of which is responsible for the development of PML, will also help reduce this risk for those patients where the use of natalizumab would be beneficial. It will also be interesting to see how the inci-dence of exposure to this virus develops over different age groups.

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Oral medications for MS on the horizon

Thefirstoralmedicationforadultmultiplesclerosis,Gilenya,wasapprovedinOctober2010bytheFDA.Until more safety data become available in adults, it is not recommended for pediatric MS patients.

8103UCSF Regional Pediatric MS Center350ParnassusAvenue,Suite908SanFrancisco,CA94117

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SAVE THE DATE!

SATURDAY, MAY 14, 2011

SIXTH ANNUAL PEDIATRIC MS FAMILY DAY

Presented by UCSF Regional Pediatric MS Center Team

and the National Multiple Sclerosis Society

Northern California Chapter

Informal gathering of families, children and teenagers living with MS and related diseases

Information - Socializing - Lunch

info: 415-353-3939,Elsa.Casillas@ucsfmedctr.org