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    You are here : Home » MS Research News » Paediatric MS

    Paediatric MS

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    MS was once thought of as just an adult disease, but, increasingly it is becoming more and more apparent that children and teenagers also are affected by this disease. To reflect this MSRC have created a seperate section devoted to this often overlooked community of people with Multiple Sclerosis.

    Below you will find the latest breaking stories on Paediatric MS Research.

    More news can be found in New Pathways Magazine, our bi-monthly publication, and also check daily at MSRC: Latest MS News

     MS In Children

    A study published June 21 in the New England Journal of Medicine sheds new light on the course of multiple sclerosis in children. The findings include:

  • Children are more likely to have a relapsing and remitting form of the disease characterised by flare-ups followed by complete recovery.
  • It takes longer for people whose MS begins in childhood to become disabled as a result of the disease.
  • Girls are more likely than boys to get MS as children.
  • Children with MS may have one key symptom called optic neuritis -- inflammation of the optic nerve that can cause vision problems.

    Further Information

  • Paediatric Multiple Sclerosis
  • Paediatric Multiple Sclerosis News
  • Resources for Children/Teens with MS
  • Children With MS
  • Teenagers With MS 
  • Fatigue, emotional functioning, and executive dysfunction in pediatric MS.

    MS DiagnosisAbstract
    Objective: Fatigue, depression, anxiety, and executive dysfunction are associated with multiple sclerosis (MS) in adults. Existing research suggests similar problems in pediatric MS, but relationships between these variables have not been investigated. This study investigates the associations between executive functioning and fatigue, emotional functioning, age of onset, and disease duration in pediatric MS.

    Methods: Twenty-six MS or Clinically Isolated Syndrome (CIS) patients, ages 7 to 18, were evaluated through a multidisciplinary demyelinating diseases clinic. Participants completed neuropsychological screening including Verbal Fluency, Digit Span, and Trail-Making Test. Parents completed rating forms of behavioral, emotional, and executive functioning. Patients and parents completed questionnaires related to the patient's quality of life and fatigue. Pearson's correlation coefficients were calculated to investigate relationships between fatigue, emotional functioning, and executive functioning, as well as to examine correlations between parent and child reports of fatigue.

    Results: Rates of parent-reported anxiety, depression, fatigue, and executive dysfunction varied widely. Means were below average on the Trail-Making Test and average on Verbal Fluency and Digit Span, though scores varied widely. Various fatigue and emotional functioning indices-but not age of onset or disease duration-significantly correlated with various performance-based measures of executive functioning.

    Conclusion: Results indicate pediatric MS is associated with some degree of fatigue, emotional difficulties, and executive dysfunction, the latter of which is associated with the two former. Notably, age of onset and disease duration did not significantly correlate with executive functioning. Results advance understanding of psychological and clinical variables related to neurocognitive outcomes in pediatric MS.

    Holland AA, Graves D, Greenberg BM, Harder LL.

    Children's Medical Center Dallas , Dallas , Texas , USA.

    Child Neuropsychol. 2012 Dec 7. & Pubmed PMID: 23216329 (14/12/12)

    Diffusion tensor analysis of paediatric MS and clinically isolated syndromes

    MS MRISummary: This new imaging study from the USA has applied diffusion imaging techniques to study connectivity in major white matter tracts in a paediatric MS population. The authors report that there are significant anisotropic abnormalities in the NAWM of major tracts in children with MS. In contrast, there were no significant changes in paediatric patients with CIS compared with controls at baseline, and DTI measures did not predict conversion to MS.

    DTI has shown focal and diffuse white matter abnormalities in adults and children with MS. Here we explore whether DTI abnormalities are present at the time of a first attack or CIS in children and whether early DTI features can predict the development of MS.

    We assessed region-of-interest and tract-based mean ADC and mean FA values for 3 major white matter pathways and NAWM in 20 children with MS, 27 children with forms of CIS, and controls. Tracts were selected by using standard region-of-interest placements on color FA maps. Identical ROIs were placed in the NAWM on b = 0 T2-weighted images to ensure that both ROIs and resulting tracts passed through NAWM. Conventional MR imaging characteristics were assessed by visual inspection. Statistical analysis compared FA and ADC values between groups by a t test. Logistic regression assessed the predictive value of DTI measures and published conventional MR imaging measures for conversion from CIS to MS.

    In paediatric patients with MS, all white matter pathways and analysis confined to the NAWM demonstrated higher mean ADC values and lower mean FA than in controls. In contrast, there were no significant differences in mean ADC and mean FA of white matter pathways in all CIS cohorts compared with controls. In the CIS cohort, none of the DTI measures in white matter pathways or in NAWM were significantly associated with conversion to RRMS in univariate or multivariate models (P > .05 in all models).

    There are significant anisotropic abnormalities in the NAWM of major tracts in children with MS. In contrast, there were no significant changes in pediatric patients with CIS compared with controls at baseline. DTI measures did not predict conversion to MS. The period between CIS and conversion to paediatric MS may represent a window of opportunity for the prevention of diffuse damage in the CNS and potentially progressive disability.

    Vishwas MS, Healy BC, Pienaar R, Gorman MP, Grant PE, Chitnis T.

    From Partners Pediatric Multiple Sclerosis Center, Massachusetts General Hospital for Children, Boston, Massachusetts; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; and Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts.

    Source: AJNR Am J Neuroradiol. 2012 Aug & Pubmed PMID: 22859275 (08/08/12)

    Research shines light on childhood multiple sclerosis

    Emily MurdochNew research suggests the number of children suffering from multiple sclerosis may be higher than previously thought.

    It remains a very rare condition and only a third of young people who have an attack will go on to develop MS in later life.

    But it can have a devastating affect on children and their families.

    One of those is 15-year-old Emily Murdoch from Cannock in Staffordshire.

    Like many girls her age, she loves horses and has been riding since she was a little girl.

    One day she hopes to represent Britain in competition, but she does not know if it will be in the Olympics or Paralympics.

    At the age of 12, Emily was diagnosed with childhood multiple sclerosis. An attack can leave her confined to a wheelchair when her legs stop working.

    She suffers from severe tiredness, muscle spasms and numb hands and legs.

    "It's not really very nice," she says "especially when my legs go on me, because it's the second time my legs have gone on me."

    "It took my left hand last time.

    "My legs get weaker. I know when my MS is bad because my legs get weak and my horse can feel it."

    Scarred brain
    At Birmingham Children's Hospital, I'm shown a scan of Emily's brain by Michael Absoud, a clinical research fellow at the University of Birmingham.

    He is one of the authors of new research into how many children are affected by the condition.

    Dr Absoud points to lighter areas on the scan which are scars left on the brain after an attack of multiple sclerosis.

    A diagnosis of MS in children is rare and sometimes controversial - not all doctors believe it exists.

    But Dr Absoud says their research suggests it is more widespread than first thought.

    "The research by itself has helped raise awareness that this disease does indeed happen in children.

    "The first presentation can be in children as young as three years old."

    Over a 13-month period, the researchers surveyed paediatricians and ophthalmologists who might see children suffering from MS-like symptoms.

    They found that MS-type attacks affected around 125 children in the UK each year. Two to three children per week were having MS-like problems with numbness or blurred vision.

    This doesn't mean every child who suffers these kind of symptoms is having an attack of MS.

    And Dr Absoud says it's thought only about a third of children who have an attack will develop the condition in later life.

    "Not all children who experience an MS-like attack will go on to develop the condition.

    "Some will recover fully and never experience similar symptoms again, while others have longer-term problems that eventually lead to a diagnosis of MS.

    "Although rare, MS can occur in childhood, but knowledge about the number of children affected by the condition, how the illness progresses and how it could best be treated is severely lacking, which is why our research is so important."

    Dr Doug Brown, head of biomedical research at the MS Society which helped fund the new research, says around one in 20 adults with MS experienced their first symptoms in childhood.

    "Historically MS has always been considered as an older person's condition, but we're now seeing people diagnosed much younger.

    "So the more we understand about childhood MS, the better health professionals can be at diagnosing the condition and offering treatment and vital support to young people and their families."

    Devastating impact
    But for the families of those children who are affected, the impact of that first diagnosis can be devastating, as Emily's mum Tracey Murdoch discovered.

    "You can't put it into words.

    "You physically don't know the 'what ifs?', 'what's happened?', 'why?'.

    "You instantly think - wheelchair, old person with MS. That's clearly not the case, as we found out when Emily was diagnosed."

    Emily is managing to keep up her riding, despite fresh attacks.

    When she is well she looks and acts like a healthy teenager. But this is a condition for which there is no known cure and only limited treatment.

    MS in children is very rare - around 10 children in every million will be diagnosed. Making that diagnosis early seems to be the key to at least slowing the progress of condition.

    And as Emily shows, with enough courage, determination and support, children with MS can go on to live a life that is at least close to normal.

    Source: BBC News © British Broadcasting Corporation 2012 (18/06/12)

    No association between chronic cerebrospinal venous insufficiency and pediatric-onset MS

    CCSVI VenogramAbstract

    Objective: Chronic cerebrospinal venous insufficiency (CCSVI) was hypothesized to play a causative role in multiple sclerosis (MS). The assessment of pediatric-onset MS (POMS) may provide a unique window of opportunity to study hypothesized risk factors in close temporal association with the onset of the disease.

    Methods: Internal jugular veins, vertebral veins and intracranial veins were evaluated with extracranial and intracranial ultrasound in 15 POMS and 16 healthy controls. Assessor’s blinding was maintained during the study. We considered subjects positive to CCSVI when at least two criteria were fulfilled.

    Results: CCSVI frequency was comparable between POMS and controls (p > 0.05). Clinical features were not significantly different between CCSVI-positive and CCSVI-negative patients.

    Conclusions: Our findings add to previous data pointing against a causative role of CCSVI in MS.

    MP Amato1, V Saia2, B Hakiki1, M Giannini1, L Pastò1, S Zecchino2, S Lori2, E Portaccio1, M Marinoni2

    1Department of Neurology, University of Florence, Florence, Italy.
    2Department of Neurological Sciences, University of Florence, Florence, Italy.

    Full Text

    Source: Multiple Sclerosis Journal Copyright © 2012 by SAGE Publications (25/04/12)

    SBU to advance research and clinical care at national pediatric MS center

    MS DiagnosisStony Brook University has received a $2.5 million gift from Robert and Lisa Lourie to advance research and clinical care at the National Pediatric Multiple Sclerosis (MS) Center at Stony Brook Long Island Children's Hospital and to establish a new state-of-the-art imaging center at Stony Brook Medicine.

    The gift will be matched by the Simons Foundation Challenge Grant, providing a total impact of $5 million. The Pediatric MS Center will be renamed the Lourie Center for Pediatric Multiple Sclerosis.

    Multiple Sclerosis historically has been viewed as an adult-onset disease. But according to the National MS Society, approximately eight-to-ten thousand children in the nation have MS. The disease in children can be difficult to diagnose. The advent of magnetic resonance imaging (MRI) and other ways to detect MS lesions have helped to secure the MS diagnosis in children. But because little is yet known on impact of the disease in children, neurologists and other MS experts still seek a consensus on MS diagnosis and treatment in children.

    The Lisa and Robert Lourie Imaging Suite will include new imaging technologies that will help Stony Brook's neuroscientists understand more about the brain and spinal cord in relation to MS, epilepsy, amyotrophic lateral sclerosis (ALS), and other neurological disorders. The first purchase for the Suite will be the Siemens Biograph mMR System, a state-of-the-art positron emission tomography (PET)/MRI scanner. The system enables physicians to simultaneously determine both structure and function of abnormalities throughout the head and body.

    "Stony Brook Medicine is rapidly becoming a national leader in academic healthcare and research," says Samuel L. Stanley, Jr., M.D., President, Stony Brook University. "The Lourie's extraordinary gift will enable us to provide the resources and environment needed to support the best researchers, and to reach new heights in pioneering research."

    "Robert and Lisa's incredible generosity will help Stony Brook Medicine advance our mission of excellence in so many ways, including both imaging and neurological disorders," says Kenneth Kaushansky, M.D., M.A.C.P., Senior Vice President, Health Sciences, and Dean, Stony Brook University School of Medicine. "The gift will allow our faculty to delve into the origins and markers of this devastating disease, hopefully leading to better diagnoses and potentially, treatments."

    "The imaging advances made possible by the PET/MRI scanner could dramatically impact the path of future research," says Lauren Krupp, M.D., Professor of Neurology, Stony Brook University School of Medicine, and Pediatric MS Program Director. Dr. Krupp explains that the use of the PET/MRI presents Stony Brook MS experts with the opportunity to pursue new avenues of research, including being able to measure the effects of MS on brain tissue at the level of individual cell types.

    The Lourie's hope is that new basic and clinical MS research at Stony Brook will lead to a cure for pediatric MS. With the multidisciplinary expert team of MS clinicians and researchers at the Center and new imaging capabilities, the team expects to advance diagnostic methods and treatments for children with MS. They also hope to unravel the mechanism by which the disease course may be reversed in pediatric cases, gaining insights that could lead to a cessation of disease progression in children and adults affected by MS.

    "There are a lot of known, valuable uses for this technology," says Robert Lourie, Ph.D., a physicist. "But it is new enough that I wouldn't be the least bit surprised if the most significant things that come out of it haven't been thought of yet."

    While the Lourie's do not have a personal connection to pediatric MS, they both feel the gift represents what they view as a responsibility to give back to important causes after being extremely successful in their careers. Dr. Lourie rose in the field of physics and eventually became a tenured Associate Professor of Physics at the University of Virginia and is now Head of Futures Research at Renaissance Technologies. Lisa Lourie is a nurse who has worked in intensive care units and with AIDS patients.

    Lisa says a "feel-good" aspect to this gift is that it incorporates their natural interests. "The research is a marriage of the bioinformatics, which is Robert's end of things, and then the clinical, which is my end of things."

    Source: News Medical (19/04/12)

    Gray matter pathology in MS: A 3-year longitudinal study in a paediatric population

    MS MRISummary: This interesting longitudinal imaging study in a paediatric MS population looks at assessing the cortical pathology differences between paediatric onset MS with adult onset MS.

    They report that cortical lesion numbers and volume as well as grey matter volume loss were greater in the adult population than paediatric population within 12 months of clinical onset.

    However both groups showed a significant increase in cortical lesions over the course of the study and analysis of the data suggests that the degree of grey matter atrophy correlate positively with cortical lesion count.



    GM pathology is considered a major determinant of disability in MS, but the comprehension of its origin and progression rate is limited by the uncertainty of dating the biologic disease onset. Thus, we planned a longitudinal study aimed at analyzing and comparing cortical pathology in pediatric and adult MS patients at clinical onset.


    Within 12 months from clinical onset, 35 patients with cMS and 57 with aMS were included in a longitudinal study. At T0, GMf and CL number and volume were analyzed. Percentages of ΔGMf and number of new CLs were assessed every year for 3 years (T1-T3). Twenty-eight age- and sex-matched NCs constituted the reference population.


    At T0, GMf did not differ between cMS and NC (P = .18), while it was lower in patients with aMS compared with both NCs (P < .001) and patients with cMS (P < .001). The number of patients with CLs, as well as CL number and volume, were higher in patients with aMS than in those with cMS (P < .001). At T3, ΔGMf was higher in both patients with cMS (1.6% ± 0.5%; range 0.7%-3.4%; P < .001) and aMS (1.6% ± 0.6%; range 0.6%-3.4%; P < .001) compared with NCs (0.7% ± 0.2%; range 0.4%-1.1%), whereas no difference was observed between patients with cMS and aMS (P = .93). ΔGMf significantly correlated with increased CL volume (cMS: r = 0.46; aMS: r = 0.48) and with the appearance of new CLs (cMS: r = 0.51; aMS: r = 0.49).


    Our findings suggest that focal (CLs) and diffuse (atrophy) GM damage are strictly associated with the biologic onset of MS, and proceed linearly and partly independently of WM pathology.

    Authors: Calabrese M, Seppi D, Romualdi C, Rinaldi F, Alessio S, Perini P, Gallo P.

    Source: AJNR Am J Neuroradiol. 2012 Mar 15 & Pubmed PMID: 22422186 (21/03/12)

    Tysabri an option for paediatric MS?

    TysabriA new study suggests that natalizumab (Tysabri, Biogen Idec/Elan) may be an effective option for the treatment of active paediatric multiple sclerosis (MS).

    The study, a cohort study of 35 pediatric patients treated out to 23 months with natalizumab, showed that the drug was safe and well-tolerated and was effective in suppressing disease activity in almost all patients.

    "I think the message is that the pediatric patient is no different in their response," to natalizumab than adult patients, senior author Giancarlo Comi, MD, director of the Department of Neurology and Institute of Experimental Neurology at the Scientific Institute and University Vita-Salute San Raffaele in Milan, Italy, told Medscape Medical News. "So there is absolutely no reason not to treat paediatric patients."

    Neurologists have not been used to treating patients with paediatric MS aggressively because there has not been a lot of experience in this population, Dr. Comi added. However, paediatric MS tends to have a more active presentation, "so it's better to have exactly the same attitude."

    The results were presented by first author Angelo Ghezzi, MD, from Centro Studi Sclerosi Multipla dell'Ospedale di Gallarate in Lombardy, Italy, on behalf of the Italian Society of Neurology's MS Study Group at the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).


    About 30% of children with paediatric MS have an inadequate response to first-line medications such as interferon beta-1a or glatiramer acetate, Dr. Ghezzi noted in his presentation. Natalizumab, which in phase 3 and phase 4 studies has shown strong suppression of clinical and magnetic resonance imaging (MRI) activity in adult patients with relapsing-remitting MS, has been shown in previous case reports and observational studies to be a "promising therapeutic option" for pediatric patients as well as adults, the authors say.

    In this non–industry-sponsored observational study, 15 Italian centers enrolled paediatric patients (younger than 18 years) with definite MS to look at the long-term safety and effect on clinical evolution of the disease of natalizumab therapy. Natalizumab has been authorised in Italy for paediatric patients with MS who have a severe or aggressive evolution of disease and no other therapeutic option, the authors note.

    Patients were treated with natalizumab if they had had at least 2 relapses in the previous 2 years and/or incomplete recovery despite treatment with interferon or glatiramer acetate; or had experienced a recent severe relapse with incomplete recovery.

    The study included 35 patients (21 girls), 25 of whom had previously been treated with at least 1 disease-modifying agent, and 13 of whom had previously been treated with more than 1 agent. Patients received a standard dose of 300 mg natalizumab every 28 days.

    Patients underwent clinical and laboratory evaluation on treatment days and had an MRI every 6 months. Follow-up was 23.8 months (standard deviation, 9.8 months), covering 24.7 infusions, and was more than a year in all cases.

    The mean age at the start of natalizumab treatment was 15 years, and the mean disease duration pretreatment was 28 months (±20 months). The mean number of attacks for these patients was 4.6, and the mean number of attacks in the year previous to natalizumab treatment was 2.6. Patients had a mean of 5.8 gadolinium-enhancing lesions at baseline.

    "We observed an impressive reduction of disease activity," the researchers note, with reductions seen in relapse rate, Extended Disability Status Scale scores, and active gadolinium-enhancing lesions on MRI compared with baseline.

    Table. Outcomes Before and After Natalizumab Treatment in Paediatric MS

    Endpoint PretreatmentPosttreatment
    Relapse rate2.60.1
    Extended Disability Status Scale scores 2.61.8
    Gadolinium-enhancing lesions5.80.4

    Only 1 clinical relapse occurred during treatment, with worsening of preexisting symptoms at the first infusion, the authors note. Thirteen patients (12%) had scans showing new T2 lesions during follow-up, and 4 patients (3.6%) had new gadolinium-enhancing lesions. Three quarters of patients, 26 (74%), remained free of new T2 or gadolinium-enhancing lesions during follow-up.

    The drug was well-tolerated: 35 mild adverse events were seen in 15 cases, most commonly headache (9) and vertigo (4); nasal congestion faringitis or tonsillitis was seen in 4 cases; and herpes zoster was seen in 3 cases.

    Patients were tested for the presence of anti–John Cunningham virus antibodies, which have been shown in adult patients to flag those at risk of developing progressive multifocal leukoencephalopathy (PML) with natalizumab therapy. Of the 35 patients, 12 were found to be positive for anti–John Cunningham virus antibodies.

    Four patients stopped natalizumab for this reason, but 8 continued with therapy because of their excellent clinical response. Natalizumab was given every 2 months in these patients, and they were monitored with MRI every 3 months. No cases of PML have been seen.

    Of the 4 patients positive for antibodies who stopped treatment, as well as 2 other patients who stopped for other reasons, 3 were treated with interferon or with glatiramer acetate. Two patients remained stable on those treatments, but 1 patient developed active lesions. Of the other 3 patients who stopped therapy, all restarted natalizumab because of the reappearance of clinical or MRI signs of disease activity. Natalizumab was given at an increased interval between administration and MRI every 3 months, instead of 6.

    "Natalizumab is a promising and quite effective drug for paediatric MS cases with aggressive evolution and poor response to first line medications," the authors conclude. Data on anti–John Cunningham virus antibodies were "reassuring," they note, "and helpful to identify patients at risk of PML."

    What's not clear at this point, Dr. Ghezzi and colleagues add, is how best to manage the withdrawal of natalizumab in paediatric patients.

    Concern About Natalizumab as First-Line Therapy

    Asked for comment on these findings, Emmanuelle Waubant, MD, PhD, associate professor of Neurology at the University of California, San Francisco, expressed concern that of the cohort, 10 of these paediatric patients had received no previous treatment with other immunomodulatory agents, but were de novo patients treated first-line with natalizumab.

    "This is not at all the practice of paediatric MS centers usually," she said. "There is a limited amount of safety data in children, so we never do that, and when I say 'we,' I can speak for the Paediatric MS Network in the United States."

    First-line choices usually include interferon beta-1a or glatiramer acetate, again based on good long-term safety data not only in adults but also in children. Although they are not specifically approved for children, she noted, these drugs have been used in that population for more than a decade.

    Although natalizumab is sometimes used in paediatric MS, she said, "in 99% of the cases, patients on natalizumab have been on a first-line disease-modifying therapy for at least 6 to 12 months before that."

    "I could understand if it was 1 in 35 patients, but 10 in 35 patients means someone in the group uses Tysabri very often as a first-line treatment. I'm not saying if it's good or bad, I'm just saying that in terms of the long-term data for safety, we just don't have it, and for children, the consequences in the long-term may be bigger than when we treat adults."

    Moreover, the mean follow-up in this report is still relatively short. "In the short term I'm not concerned, but 4 or 5 years down the line, what's the safety for my patient?"

    Lessons From Paediatric MS

    At the meeting, Dr. Waubant, who specializes in paediatric MS, also gave a talk on what the study of paediatric patients can teach neurologists about how to approach their adult MS patients.

    "Paediatric MS gives us a unique window of opportunity to study the effect of age on immune and neurologic maturation that may improve our understanding of adult-onset MS," Dr. Waubant noted.

    "When we are looking at young patients we are touching on phenomena such as maturation of the central nervous system [and] maturation of the immune system, and it gives us a better understanding of what the respective role these 2 have on the course of the disease," she told Medscape Medical News. "We can learn from that to extrapolate the understanding to adult MS, and possibly come up with new strategies to treat patients better."

    Studying paediatric cases of MS also provides an opportunity to study risk factors for the disease much closer to disease onset, perhaps mitigating the confounding factors that might mask these relationships.

    "Patients are closer to the exposures for the risk factors, and their parents can give us a lot of information about those possible risk factors," she added. "If we're thinking about infections, or diet, or toxins, or stress — what happened during the pregnancy or just after the pregnancy — all these are important to consider, and it's hard to get to that when we're studying MS in adults."

    Because of the current overlap of risk factors in paediatric and adult-onset MS, "newly identified risk factors in paediatric MS are expected to apply to adult MS as well," she said.

    Dr. Waubant is principal investigator of a new case-control study that aims to examine these kinds of exposures. The study, called Genetic and Environmental Risk Factors for Paediatric MS and Interactions, is funded by the National Institutes of Health and is now ongoing at 10 centres in the United States. They have a recruitment target of 600 cases of paediatric MS within 2 years of onset, and 1200 matched control patients.

    "We hope to have exciting data in the next 4 years from now," she said.

    The study was not sponsored by any pharmaceutical company. Dr. Ghezzi received honoraria for speaking from Bayer-Schering, Biogen-Dompè, Merck-Serono, and Novartis; honoraria for consultancy from Actelion, Merck-Serono, and Novartis; and support for participation in national and international congresses from Bayer-Schering, Biogen-Dompè, Merck-Serono, Novartis, and sanofi-aventis. Dr. Comi received personal compensation form Bayer-Schering, Serono Symposia International Foundation, Merck-Serono International, TEVA Pharmaceutical Industries Ltd, sanofi-aventis, and Biogen-Dompè for consulting services and received personal compensation from TEVA Pharmaceutical Industries Ltd, sanofi-aventis, Serono Symposia International Foundation, Biogen-Dompè, and Bayer-Schering for speaking activities. TEVA Pharmaceutical Industries Ltd, sanofi-aventis, Serono Symposia International Foundation, Biogen-Dompè, and Bayer-Schering have given Dr. Comi supported for the costs of travelling and lodging related to speaking activities. Disclosures for the other coauthors are published in the abstract. Dr. Waubant has disclosed no relevant financial relationships.

    5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS): Abstract 61.

    Source: Medscape Today Copyright © 1994-2011 by WebMD LLC. (08/11/11)

    MRI parameters for prediction of MS diagnosis in children with acute CNS demyelination

    MS MRISummary

    Multiple sclerosis (MS) diagnostic criteria incorporate MRI features that can be used to predict later diagnosis of MS in adults with acute CNS demyelination. To identify MRI predictors of a subsequent MS diagnosis in a paediatric population, we created a standardised scoring method and applied it to MRI scans from a national prospective incidence cohort of children with CNS demyelination.

    Clinical and MRI examinations were done at the onset of acute CNS demyelination and every 3 months in the first year after that, and at the time of a second demyelinating attack. MS was diagnosed on the basis of clinical or MRI evidence of relapsing disease.

    Baseline MRI scans were assessed for the presence of 14 binary response parameters. Parameters were assessed with a multiple tetrachoric correlation matrix. Univariate analyses and multivariable Cox proportional hazards models were used to identify predictors of MS.

    Between Sept 1, 2004, and June 30, 2010, 332 children and adolescents were assessed for eligibility. 1139 scans were available from 284 eligible participants who had been followed up for 3·9 (SD 1·7) years. 57 (20%) were diagnosed with MS after a median of 188 (IQR 144—337) days. Seven of 14 binary response parameters were retained. The presence of either one or more T1-weighted hypointense lesions (hazard ratio 20·6, 95% CI 5·46—78·0) or one or more periventricular lesions (3·34, 1·27—8·83) was associated with an increased likelihood of MS diagnosis (sensitivity 84%, specificity 93%, positive predictive value 76%, negative predictive value 96%).

    Risk for MS diagnosis was highest when both parameters were present (34·27, 16·69—70·38). Although the presence of contrast enhancement, cerebral white matter, intracallosal, and brainstem lesions was associated with MS in the univariate analyses, these parameters were not retained in the multivariable models.

    Specific MRI parameters can be used to predict diagnosis of MS in children with incident demyelination of the CNS. The ability to promptly identify children with MS will enhance timely access to care and will be important for future clinical trials in paediatric MS.

    Canadian Multiple Sclerosis Scientific Research Foundation.

    Source: The Lancet Neurology Copyright © 2011 Elsevier Limited (07/11/11)

    Progressive multifocal leukoencephalopathy associated with natalizumab in paediatric MS

    TysabriBackground: In the pediatric Multiple Sclerosis (MS) population large and controlled studies on safety and efficacy of Natalizumab have not yet been performed. In literature there have been no cases of Natalizumab-related Progressive Multifocal Leukoencephalopathy (PML) reported in paediatric population with MS.

    Case Report: A 14-year-old girl presented in October 2009 diplopia, gait ataxia, vomiting and impaired mentation, preceded by asthenia, fever and left sensory loss lasting for 3 days, 1 month earlier. MRI showed a diffuse leukoencephalopathy with large lesions in brainstem, semioval centers and spinal cord with diffuse gadolinium enhancement. The IgG Index was increased. After treatment with i.v. Methylprednisolone (MP) she improved.

    Initial diagnosis was ADEM. In December 2009 she presented behavioural changes, ataxia, strabismus and urinary incontinence. Brain MRI showed new large lesions with ring enhancement. She was treated with MP and high dose i.v. immunoglobulins for 5 days without efficacy. She underwent 3 Mitoxantrone (8 mg/sqm) monthly infusions and then 8 plasma exchanges, with partial recovery only in mental function. MRI showed new demyelinating areas with ring enhancement. A 10 d MP course was followed by improvement in motor and mental functions; apraxia and urinary incontinence persisted.

    Final diagnosis was of malignant MS. She was treated with monthly Natalizumab infusions from May 2010 to December 2010, with partial efficacy. Antibodies against Natalizumab were negative. Her parents refused autologous bone marrow transplantation.

    In February 2011 the girl had a clinical relapse with stable MRI. She was treated with Natalizumab (one infusion) and i.v. MP. Brain MRI in March 2011 showed new areas in left frontal lobe, some subcortical with enhancement. The girl had further deterioration in cognitive function. Test for JC virus antibodies was positive. Assuming a diagnosis of PML Natalizumab was stopped and lumbar puncture was performed. PCR for JC virus DNA revealed over 140 copies and diagnosis of PML was confirmed.

    Conclusions: This case of paediatric MS is extremely aggressive and no treatment was really effective to stabilize the disease. The girl had a cognitive impairment from the beginning of the disease and worsening of it is the only signal of PML. Further studies are needed to assess the efficacy and safety of Natalizumab in paediatric MS population and to identify clinical and radiological parameters for early diagnosis of PML.

    M di Ioia, D. Farina, G. De Luca, D. Travaglini, V. Di Tommaso, E. Pietrolongo, A. Lugaresi (Chieti, IT)

    Maria Di Ioia is involved in clinical trials of Merck Serono S.A – Geneva and Teva Neuroscience Deborah Farina has received researcher grant from: Merck Serono S.A. – Geneva, Biogen-Dompè and is involved in clinical trials of the same company, plus GlaxoSmithKline, Biogen-Dompé, Bayer Schering, Novartis and Teva. Giovanna De Luca has received a researcher grant from: Merck Serono S.A. – Geneva and is involved in clinical trials of the same company, plus GlaxoSmithKline, Biogen-Dompé, Bayer Schering, Novartis and Teva. Daniela Travaglini is involved in clinical trials of GlaxoSmithKline, Biogen-Dompé, Bayer Schering, Merck-Serono, Novartis and Teva. Valeria Di Tommaso is involved in clinical trials of GlaxoSmithKline, Biogen-Dompé, Bayer Schering, Merck-Serono, Novartis and Teva. Erika Pietrolongo is involved in clinical trials of Merck-Serono, Novartis, Sanofi-Aventis and Teva. Alessandra Lugaresi has received research and travel support or speaker fees from Biogen-Dompé, Bayer Schering, Merck-Serono, Novartis, Sanofi-Aventis and Teva.

    Source: 5th Joint triennial congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis Amsterdam, The Netherlands 19.10.2011 - 22.10.2011 (31/10/11)

    Paediatric MS: examining utility of the McDonald 2010 criteria

    MS DiagnosisSummary: This relatively small but interesting study from the UK aimed to assess the utility of McDonald 2010 criteria in comparison with 2007 International Paediatric Multiple Sclerosis Study Group (IPMSSG)-recommended criteria for the diagnosis of paediatric multiple sclerosis (PMS).

    The authors conducted a retrospective analysis of 38 cases of clinically definite relapsing remitting MS from three UK clinics. They found that on baseline scans IPMSSG dissemination in space (DIS) criteria were fulfilled in 68% of scans and McDonald DIS criteria in 84%. The authors therefore suggest that the 2010 McDonald criteria appear more sensitive than IPMSSG and may allow PMS diagnosis at first presentation of CIS in at least a half of cases.

    The new McDonald 2010 criteria have been recommended in paediatric multiple sclerosis (PMS).

    We aimed to assess the utility of McDonald 2010 criteria in comparison with 2007 International Paediatric Multiple Sclerosis Study Group (IPMSSG)-recommended criteria for PMS diagnosis.

    Retrospective analysis of 38 PMS cases from three UK demyelination clinics was conducted. Dissemination in space (DIS) and time (DIT) for both McDonald and IPMSSG criteria were noted on initial and follow-up magnetic resonance imaging (MRI).

    At first MRI scan, IPMSSG DIS criteria were fulfilled in 68% of scans and McDonald DIS criteria in 84%.

    In total, 11/18 children given gadolinium contrast fulfilled both McDonald DIS and DIT criteria on initial scan.

    The 2010 McDonald criteria appear more sensitive than IPMSSG and may allow PMS diagnosis at first presentation of CIS in at least a half of cases.

    Authors: Sedani S, Lim M, Hemingway C, Wassmer E, Absoud M.

    Sources: Pubmed PMID: 22013145 & Mult Scler. 2011 Oct 19 (26/10/11)

    Shift work may put teens at risk of Multiple Sclerosis

    Teenagers and MSWorking overnight or odd shifts may increase teenagers’ risk of developing multiple sclerosis, according to the results of an observational study.

    Researchers from Sweden who uncovered the link said interruption of circadian rhythms and disruption of normal sleep patterns may be partially responsible for the added risk.

    In conducting the study, published in the Oct. 18 issue of Annals of Neurology, researchers examined two population-based studies of Swedish residents aged 16 to 70 (one with incident cases and one with prevalent cases) to compare the number of cases of multiple sclerosis among those who did and did not work overnight or shift hours on a regular or alternating basis during their teens.

    Among the incident cases, the investigators found those who worked overnight hours for three years or more before the age of 20 were twice as likely to develop multiple sclerosis as those who never worked night shifts. Among the prevalent cases, they noted, the teens who worked overnight hours were slightly more than twice as likely to develop the disorder commonly called MS.

    “Our analysis revealed a significant association between working shift at a young age and occurrence of MS,” Dr. Anna Karin Hedstrom, of the Karolinska Institute in Stockholm, said in a journal news release. “Given the association was observed in two independent studies strongly supports a true relationship between shift work and disease risk.”

    The researchers explained the sleep restriction associated with working the night shift has already been shown to increase the risk for certain health problems, including heart disease, thyroid disorders and cancer, likely by interfering with melatonin secretion and increasing inflammatory responses.

    The authors pointed out that since MS is a central nervous system autoimmune inflammatory disorder that is linked to a person’s environment, other lifestyle risk factors, such as sleep loss due to shift work, should also be considered.

    The study authors noted that more research is needed to explain why the disruption of circadian rhythm and sleep loss increase teenagers’ risk for developing MS.

    Source: Copyright © 2011 Health Media Ventures, Inc (18/10/11)

    Diffusion tensor imaging and cognitive speed in children with MS

    Diffusion Tensor ImagingSummary: The study aims to correlate diffusion tension imaging (DTI) findings with disease activity, lesion burden, and cognitive processing speed in children.

    MS participants displayed lower fractional anisotropy (FA) values in corpus callosum and in normal-appearing white matter (NAWM) versus controls. Higher lesion volumes correlated with reduced FA in the corpus callosum and hemispheric NAWM but DTI metrics did not correlate with disability. FA values in corpus callosum regions did however correlate with cognitive speed tasks in MS participants only. Overall the authors conclude that the results suggest an early onset tissue pathology in MS and illustrate its functional consequence.

    To compare white matter (WM) integrity in children with MS and healthy children using diffusion tensor imaging (DTI), and correlate DTI findings with disease activity, lesion burden, and cognitive processing speed.

    Fractional anisotropy (FA) and mean diffusivity (MD) in normal-appearing white matter (NAWM) were measured in four corpus callosum (CC), eight hemispheric regions, and the normal-appearing thalamus of 33 children and adolescents with MS and 30 age-matched healthy controls. Images were acquired on a GE LX 1.5T scanner. DTI parameters used were 25 directions, b=1000s/mm(2), and 5mm slice thickness. MS patients had T2 lesion volumes and Expanded Disability Status Scale (EDSS) scores were measured; all participants underwent two speeded cognitive tasks (Visual Matching and Symbol Digit Modalities Test (SDMT)).

    MS participants displayed lower FA values in the genu (p<0.005), splenium (p<0.001) and in NAWM of bilateral parietal, temporal, and occipital lobes (p<0.001) versus controls. FA and MD in the thalamus did not differ between groups. Higher lesion volumes correlated with reduced FA in CC and hemispheric NAWM. DTI metrics did not correlate with EDSS. FA values in CC regions correlated with Visual Matching (p<0.001) and SDMT (p<0.005) in MS participants only.

    DTI analyses indicate widespread NAWM disruption in children with MS-with the degree of abnormality correlating with impaired cognitive processing speed. These findings support an early onset tissue pathology in MS and illustrate its functional consequence.

    Authors: Bethune A, Tipu V, Sled JG, Narayanan S, Arnold DL, Mabbott D, Rockel C, Ghassemi R, Till C, Banwell B.

    Source: Pubmed 21821263 & J Neurol Sci. 2011 Aug 5. Copyright © 2011 Elsevier B.V. (10/08/11)

    Cognitive impairment linked to reduced brain size in children with MS

    Paediatric MSChildren who suffer cognitive impairment from Multiple Sclerosis (MS) are more likely to have less brain matter, according to a study by researchers from York University, The Hospital for Sick Children, and McGill University.

    Researchers found that cognitive impairment occurs in approximately 30 percent of children and teens with MS; reduced processing speed is most commonly observed, even early in the disease process. These deficits can impact overall efficiency of cognitive networks and disrupt learning of new information, the study says.

    “More significantly, we found the severity of cognitive dysfunction to be strongly correlated to a reduction in size in key brain regions, including the thalamus and corpus callosum, and less strongly influenced by inflammatory activity, as detected by lesion volume in the brain,” says the study’s lead author, Christine Till, assistant professor of psychology in York’s Faculty of Health. “This suggests a link between cognitive impairment and the neurodegenerative component of MS, and highlights the important impact of the disease on deep grey matter structures and related neural networks,” she says.

    Detailed neuropsychological evaluations and high-quality MRI scans were performed on 35 patients with pediatric onset MS who were recruited from the Pediatric Demyelinating Disease Clinic at Toronto’s Hospital for Sick Children. Researchers compared their findings to results from healthy children, who were of similar age, sex, and parental education level.

    MRI results showed that children with MS have overall smaller brain volumes than expected for their age. Regional analysis taking into account differences in head size showed that the thalamus, a key brain structure involved in attention, arousal, and memory, was reduced by 11.9 percent in the MS patients. The corpus callosum, which is the largest white matter tract in the brain and important for transmitting information between brain hemispheres, was reduced by five percent.

    “A key component of MS onset during childhood relates to its effect on the developing brain,” says Till. “Overall, our findings suggest that the young age of childhood-onset MS patients does not protect them from the negative impact of the disease. We know that the earlier a patient develops MS, the greater likelihood their language development will be negatively impacted,” she says.

    Approximately 24 to 40 percent of MS patients in the study showed impaired cognitive performance on measures of processing speed and visuomotor integration (e.g. copying designs). Impairments were also noted in complex attention (e.g. simultaneously attending to multiple stimuli), visual-spatial abilities, expressive language, and executive functions such as shifting attention back and forth between two stimuli, planning and organizing. In addition, the children identified with global cognitive impairment tended to be male and to have the disease for a longer duration.

    “Interestingly, physical disability did not correlate with cognitive impairment, suggesting that cognitive dysfunction can be present in the absence of physical disability,” Till says.

    The current research is part of a three-year study investigating the long-term effects of MS on cognitive performance. Serial analyses of MRI scans are currently underway to examine whether cognitive decline reflects the progressive neurodegenerative aspect of MS in children and teens.

    “MS is increasingly diagnosed in childhood, which makes the need to understand pediatric implications of the disease all the more pressing,” says Till. “We need to fully comprehend how the disease functions in its earliest stages in order to devise interventions that can help [pediatric patients].”

    The paper, “MRI Correlates of Cognitive Impairment in Childhood-Onset Multiple Sclerosis,” was published in the journal Neuropsychology in May 2011. Researchers from the Hospital for Sick Children and the Montreal Neurological Institute contributed to this study, which was supported by the MS Society of Canada.

    Source: York University (17/06/11)

    Common viruses associated with lower pediatric MS risk

    Paediatric MSAbstract

    Background: Because common viruses are encountered during childhood, pediatric multiple sclerosis (MS) offers a unique opportunity to investigate the influence of these viruses on disease susceptibility and the interactions between seroprevalence and select HLA genotypes. We studied seroprevalence for Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV) type 1 and HLA-DRB1*1501/1503 status as predictors of pediatric MS.

    Methods: This was a retrospective analysis of prospectively collected demographic, clinical, and biologic data in subjects up to 18 years of age with early MS, control subjects seen at the same regional referral pediatric MS clinics, and additional healthy pediatric control subjects.

    Results: Patients with early pediatric MS (n = 189) and pediatric control subjects (n = 66) were tested. Epstein-Barr nuclear antigen-1 seropositivity was associated with an increased odds of MS (odds ratio [OR] 3.78, 95% confidence interval [CI] 1.52–9.38, p = 0.004) in analyses adjusted for age, sex, race, ethnicity, and HLA-DRB1*1501/1503 status. In multivariate analyses including EBV status, a remote infection with CMV (OR 0.27, 95% CI 0.11–0.67, p = 0.004) was associated with a lower risk of developing MS. Although a remote infection with HSV-1 was not associated with an increased odds of MS, a strong interaction was found between HSV-1 status and HLA-DRB1 in predicting MS (p < 0.001). HSV-1 was associated with an increased risk of MS in those without a DRB1*15 allele (OR 4.11, 95% CI 1.17–14.37, p = 0.03), whereas the effect was reversed in those who were DRB1*15-positive (OR 0.07, 95% CI 0.02–0.32, p = 0.001).

    Conclusions: These findings suggest that some infections with common viruses may in fact lower MS susceptibility. If this is confirmed, the pathways for risk modification remain to be elucidated.


    Study funding: The Pediatric MS Network, initiated and sponsored by the National Multiple Sclerosis Society, includes the following centers: University of California, San Francisco, Stony Brook, Buffalo, University of Alabama Birmingham, Harvard University, and the Mayo Clinic. Dr. Mowry has a National MS Society Sylvia Lawry Fellowship Award and an NIH K23NS067055. Dr. Waubant is also supported by the Nancy Davis Foundation. Dr. James is supported by NIH RR015577, AI082714, U19AI082714, and AR053483. Dr. Oksenberg is supported by NMSS RG2901D9/1.

    E. Waubant, MD, E.M. Mowry, MD, L. Krupp, MD, T. Chitnis, MD, E.A. Yeh, MD, N. Kuntz, MD, J. Ness, MD, D. Chabas, MD, J. Strober, MD, J. McDonald, BS, A. Belman, MD, M. Milazzo, NP, M. Gorman, MD, B. Weinstock-Guttman, MD, M. Rodriguez, MD, J.R. Oksenberg, MD, J.A. James, MD

    Source: Neurology Copyright © 2011 by AAN Enterprises, Inc (13/06/11)

    Children with MS may be at increased risk of obesity

    Childhood ObesityIn addition to the health problems children with multiple sclerosis face, a risk of obesity has entered the picture.

    A new study conducted by pediatric MS specialists at the University at Buffalo has found that children with multiple sclerosis and other pediatric demyelinating disorders are at increased risk of childhood obesity, compared to children without these disorders.

    The findings build on a study done by other researchers showing an association between obesity in adolescence and MS in adulthood, but this appears to be the first study to evaluate obesity in relation to pediatric demyelinating disorders.

    Results of the current research were presented at a poster session at the 2011 American Academy of Neurology meeting held in April in Honolulu. E. Ann Yeh, MD, UB assistant professor of neurology and a pediatric MS specialist in the UB School of Medicine and Biomedical Sciences, is first author.

    "We found that rates of obesity were high in children with demyelinating disorders and were especially prevalent in boys," says Yeh. "Boys with demyelinating disorders were almost twice as likely to have a BMI greater than the 95th percentile than boys in the control group."

    The findings are based on the body mass index of 186 children: 41 with MS, 34 with acute disseminated encephalomyelitis (ADEM), a monophasic demyelinating disorder seen primarily in childhood; 15 with clinically isolated syndrome, an individual's first demyelinating episode (distinct from ADEM); eight with recurrent optic neuritis (RON), inflammation of the optic nerve, and 87 children with other neurological disorders who served as controls.

    Although obesity has been linked to heart disease and diabetes, among other illnesses, little is known about its relationship to inflammatory demyelinating disorders.

    "Increasing rates of childhood obesity have been reported widely in the media and in medical journals," says Yeh, "but no information is available on the relationship between obesity and childhood-onset demyelinating disorders."

    Subjects in the current study were patients of UB's Pediatric MS and Demyelinating Disorders Center of Excellence at Women and Children's Hospital of Buffalo. Data were collected prospectively between January 2003 and October 2010 in patients under the age of 18.

    BMI scores, percentile of age scores, and a measure called BMI z-scores were calculated at disease presentation, using a standardized pediatric BMI calculator. (A Z-Score is a statistical measure that shows how a single data point compares to normal data.)

    Results showed that rates of overweight and obese children were greater in the demyelinating groups than in the control group, and that boys in the demyelinating groups were twice as likely as girls to have a BMI in the 95th percentile or greater.

    "These findings underscore the need for attention to the nutritional and physical needs of children with these disorders," states Yeh. "Comprehensive programs oriented toward the prevention of obesity in all children are needed, but we also need further studies to help define the relationship between obesity and risk for demyelinating disorders."

    Murali Ramanathan, PhD, UB professor of pharmaceutical sciences and neurology, and

    Bianca Weinstock-Guttman, PhD, UB associate professor of neurology, both associated with the Pediatric MS and Demyelinating Disorders Center of Excellence, also contributed to the research.

    The study was funded in part by the Children's Guild Foundation of Buffalo. Clinical care at the Pediatric MS Center of Excellence is supported by the National MS Society.

    Source: University at Buffalo © 2011 University at Buffalo.  (16/05/11)

    MRI correlates of cognitive impairment in childhood-onset MS


    Objective: Brain MRI measures were correlated with neuropsychological function in 35 pediatric-onset multiple sclerosis (MS) patients and 33 age- and sex-matched healthy controls.

    Method: Mean age of MS patients was 16.3 ± 2.3 years with average disease duration of 4.3 ± 3.1 years. Cortical gray matter, thalamic, and global brain volumes were calculated for all participants using a scaling factor computed using normalization of atrophy method to normalize total and regional brain volumes for head size. T1- and T2-weighted lesion volumes were calculated for MS patients.

    Results: Cognitive impairment (CI) was identified in 29% of the MS cohort. Cognitive deficits predominantly involved attention and processing speed, expressive language, and visuomotor integration. Relative to controls, the MS group showed significantly lower thalamic volume (p < .001), total brain volume (p < .008), and gray matter volume (p < .015). Corpus callosum area and thalamic volume differentiated patients identified as having CI from those without CI (p < .05). Regression models controlling for disease duration and age indicated that thalamic volume accounted for significant incremental variance in predicting global IQ, processing speed, and expressive vocabulary (ΔR2 ranging from .43 to .60) and was the most robust MRI predictor of cognition relative to other MRI metrics.

    Conclusions: The robust association between cognitive function and reduced size of thalamus and global brain volume in pediatric-onset MS patients implicate neurodegenerative processes early in the disease course, and suggest that plasticity of an immature central nervous system is not sufficient to protect patients from the deleterious consequences of MS on cognitive neural networks.

    Full Article:  Neuropsychology, Vol 25(3), May 2011, 319-332. doi: 10.1037/a0022051 

    Source: COMD News (06/05/11)

    Clinical, environmental, and genetic determinants of MS in children with acute demyelination

    MS DiagnosisSummary

    HLA-DRB1*15 genotype, previous infection with Epstein-Barr virus, and vitamin D insufficiency are susceptibility factors for multiple sclerosis, but whether they act synergistically to increase risk is unknown. We aimed to assess the contributions of these risk factors and the effect of established precursors of multiple sclerosis, such as brain lesions on MRI and oligoclonal bands in CSF at the time of incident demyelination, on development of multiple sclerosis in children.

    In our prospective national cohort study, we assessed children who presented with incident CNS demyelination to any of the 16 paediatric health-care facilities or seven regional health-care facilities in Canada. We did univariate and multivariable analyses to assess contributions of HLA-DRB1*15, Epstein-Barr virus, vitamin D status, MRI evidence of brain lesions, and CSF oligoclonal bands as determinants of multiple sclerosis. We used classification and regression tree analyses to generate a risk stratification algorithm for clinical use.

    Between Sept 1, 2004, and June 30, 2010, we screened 332 children of whom 302 (91%) were eligible and followed-up for a median of 3·14 years (IQR 1·61—4·51). 63 (21%) children were diagnosed with multiple sclerosis after a median of 127 days (99—222). Although the risk of multiple sclerosis was increased with presence of one or more HLA-DRB1*15 alleles (hazard ratio [HR] 2·32, 95% CI 1·25—4·30), reduced serum 25-hydroxyvitamin D concentration (HR per 10 nmol/L decrease 1·11, 1·00—1·25), and previous Epstein-Barr-virus infection (HR 2·04, 0·99—4·20), no interactions between these variables were detected on multivariate analysis. Multiple sclerosis was strongly associated with baseline MRI evidence of one or more brain lesion (HR 37·9, 5·26—273·85) or CSF oligoclonal bands (6·33, 3·35—11·96), suggesting established disease. One patient diagnosed with multiple sclerosis had a normal MRI scan, and therefore sensitivity of an abnormal MRI scan for multiple sclerosis diagnosis was 98·4%.

    Risk of multiple sclerosis in children can be stratified by presence of HLA-DRB1*15 alleles, remote Epstein-Barr virus infection, and low serum 25-hydroxyvitamin D concentrations. Similar to previous studies in adults, brain lesions detected on MRI and CSF oligoclonal bands in children are probable precursors to the clinical onset of multiple sclerosis. Children with a normal MRI are very likely to have a monophasic illness.

    Canadian Multiple Sclerosis Scientific Research Foundation.

    Full Article.

    Dr Brenda Banwell MD a b , Amit Bar-Or MD c, Prof Douglas L Arnold MD d, Prof Dessa Sadovnick PhD e, Sridar Narayanan PhD d, Melissa McGowan MSc b, Julia O'Mahony MSc b, Sandra Magalhaes MSc c, Heather Hanwell MSc b f, Prof Reinhold Vieth PhD f, Raymond Tellier MD g, Thierry Vincent PhD h, Giulio Disanto MD i, Prof George Ebers MD i, Katherine Wambera MD j, Mary B Connolly MBBCh k, Prof Jerome Yager MD l, Jean K Mah MD m, Fran Booth MD n, Guillaume Sebire MD o, David Callen MD p, Brandon Meaney MD p, Marie-Emmanuelle Dilenge MD q, Anne Lortie MD r, Daniela Pohl MD s, Asif Doja MD s, Sunita Venketaswaran MD s, Simon Levin MD t, E Athen MacDonald MD u, David Meek MD v, Ellen Wood MD w, Noel Lowry MD x, David Buckley MD y, Conrad Yim MD z, Mark Awuku MD aa, Pamela Cooper MD ab, François Grand'Maison MD ac, J Burke Baird MD ad, Virender Bhan MD ae, Ruth Ann Marrie MD af

    a Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
    b Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
    c Neuroimmunology Unit and Experimental Therapeutics Program, Montreal Neurological Institute, McGill University, Montreal, QC, Canada
    d McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada
    e Department of Neurology and Division of Medical Genetics, University of British Columbia, BC, Canada
    f Department of Nutritional Sciences, University of Toronto, and Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada
    g Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada
    h Département d'Immunologie, Hôpital Saint-Eloi, CHU de Montpellier, Montpellier, France
    i Wellcome Trust Centre for Human Genetics, Department of Clinical Neurology, University of Oxford, Oxford, UK
    j Victoria General Hospital, Victoria, BC, Canada
    k Children's Hospital of British Columbia, Vancouver, BC, Canada
    l Stollery Children's Hospital, Edmonton, AB, Canada
    m Alberta Children's Hospital, Calgary, AB, Canada
    n The Children's Hospital of Winnipeg, Winnipeg, MB, Canada
    o Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada
    p McMaster Children's Hospital, Hamilton, ON, Canada
    q The Montreal Children's Hospital, Montreal, QC, Canada
    r Centre Hospitalier Universitaire de Sainte-Justine, Montreal, QC, Canada
    s Children's Hospital of Eastern Ontario, Ottawa, ON, Canada
    t Children's Hospital of Western Ontario, London, ON, Canada
    u Queen's University, Kingston, ON, Canada
    v Saint John Regional Hospital, Saint John, NB, Canada
    w IWK Health Centre, Halifax, NS, Canada
    x Royal University Hospital, Saskatoon, SK, Canada
    y Janeway Children's Health and Rehabilitation Centre, St John's, NL, Canada
    z Trillium Health Centre, Mississauga, ON, Canada
    aa Windsor Regional Hospital, Windsor, ON, Canada
    ab Rouge Valley-Centenary Hospital, Scarborough, ON, Canada
    ac Hôpital Charles LeMoyne, Montreal, QC, Canada
    ad Sudbury Regional Hospital, Sudbury, ON, Canada
    ae Dalhousie MS Research Unit, Halifax, NS, Canada
    af Department of Internal Medicine, Winnipeg Health Sciences Center, University of Manitoba, Winnipeg, MB, Canada

    Source: The Lancet Neurology Copyright © 2011 Elsevier Limited. (21/04/11)

    MS therapies in pediatric patients with refractory MS

    Disease Modifying DrugsBackground:  Currently available disease-modifying therapies (DMTs) are known to be only partially effective in adults with multiple sclerosis (MS). Little is known about pediatric patients with MS who experience refractory disease while receiving first-line DMTs.

    Objective:  To assess the occurrence and management of refractory disease in a group of pediatric patients with MS treated with first-line DMTs approved for adult patients within a network of pediatric MS centers in the United States.

    Design, Setting, and Patients:  A multicenter, retrospective, longitudinal, open-label study design involving record review of 258 patients with pediatric-onset MS (68.6% female; mean [SD] age at disease onset, 13.2 [3.5] years; range of age at onset, 2.0-17.9 years) who were seen at 6 pediatric MS centers in the United States.

    Intervention:  We evaluated medication changes owing to refractory disease in cases of pediatric-onset MS.

    Main Outcome Measure:  Disease stability as represented by lack of medication change for breakthrough disease.

    Results:  Records of 258 children with a confirmed diagnosis of MS and exposure to DMTs were reviewed. Interferon beta (prescribed to 200 of 258 children [77.5%]) and glatiramer acetate (prescribed to 53 of 258 children [20.5%]) were the 2 most frequently used first-line DMTs. Overall, 144 children (55.8%) continued receiving 1 therapy, while 65 (25.2%), 29 (11.2%), and 20 (7.8%) received 2, 3, or 4 or more sequential therapies, respectively, during a mean (SD) observation period of 3.9 (2.8) years. Second-line DMT use was restricted to interferon beta and glatiramer acetate in 203 children (78.7%), whereas other treatments such as broad-spectrum chemotherapies (cyclophosphamide, mitoxantrone hydrochloride), natalizumab, corticosteroids (monthly), and daclizumab were used at some point during the observation period for disease management in 55 children (21.3%). Hispanic children were more likely to experience breakthrough disease while receiving first-line DMTs than non-Hispanic children.

    Conclusion:  Although switching between first-line DMTs may be effective in pediatric patients with disease that is refractory to initial treatment, a subset of patients may require second-line therapeutic interventions.

    E. Ann Yeh, MD; Emmanuelle Waubant, MD, PhD; Lauren B. Krupp, MD; Jayne Ness, MD, PhD; Tanuja Chitnis, MD; Nancy Kuntz, MD; Murali Ramanathan, PhD; Anita Belman, MD; Dorothee Chabas, MD, PhD; Mark P. Gorman, MD; Moses Rodriguez, MD; John Robert Rinker II, MD; Bianca Weinstock-Guttman, MD; for the National Network of Pediatric MS Centers of Excellence

    Author Affiliations: Pediatric Multiple Sclerosis and Demyelinating Disorders Center of the Jacobs Neurological Institute, Women and Children's Hospital of Buffalo (Drs Yeh, Ramanathan, and Weinstock-Guttman) and Departments of Neurology (Drs Yeh, Ramanathan, and Weinstock-Guttman) and Pharmaceutical Sciences (Dr Ramanathan), State University of New York, Buffalo, and National Pediatric MS Center, Department of Neurology, State University of New York, Stony Brook (Drs Krupp and Belman); Regional Pediatric Multiple Sclerosis Center, Department of Neurology, University of California, San Francisco (Drs Waubant and Chabas); Center for Pediatric Onset Demyelinating Disorders, University of Alabama at Birmingham (Drs Ness and Rinker); Partners Pediatric Multiple Sclerosis Center, Massachusetts General Hospital for Children, Boston (Drs Chitnis and Gorman); Mazza Foundation Neuromuscular Program, Children's Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (Dr Kuntz); and Pediatric Multiple Sclerosis Center, Mayo Clinic, Rochester, Minnesota (Dr Rodriguez).

    Full Article Arch Neurol. 2011;68(4):437-444. doi:10.1001/archneurol.2010.325

    Source: Archives Of Neurology © 2011 American Medical Association (12/04/11)

    Multiple Sclerosis: risk factors in children

    Paediatric MSCanadians have one of the highest rates of Multiple Sclerosis (MS) in the world with approximately 1,000 new cases diagnosed each year. Primarily striking in adulthood, physicians and researchers with the Canadian Pediatric Demyelinating Diseases Network (CPDDN), a multi-institutional and multidisciplinary group, have found that MS is being increasingly diagnosed in children. 

    A study by the CPDDN published in the journal Neurology, identifies a particular gene involved in the immune response that puts certain children at a higher risk of developing MS.

    In children, an initial attack of demyelination (acquired demyelinating syndrome [ADS] in the central nervous system) often remains a single, isolated episode.  However, in at least 20 % of children it represents the first clinical attack of MS. This contrasts with adult-onset MS, where most individuals presenting with acute demyelination are subsequently diagnosed with MS. Demyelination is the destructive loss of myelin - the protective covering that insulates and supports nerve cells - damaging the cells' ability to receive and transmit signals in the body.

    "The uncertainty of the diagnosis understandably creates a lot of anxiety for children and their families," says Dr. Amit Bar-Or, neurologist and lead investigator at The Montreal Neurological Institute and Hospital - The Neuro, McGill University. "Having the tools to distinguish ADS and MS is important." Researchers at The Neuro in collaboration with researchers at the SickKids in Toronto and international colleagues therefore wanted to identify the risk factors in the 20% of children who go on to develop MS, and to investigate if the risk factors and the disease biology are the same in both children and adults.

    In adults, complex interactions between genetic and environmental factors contribute to risk and the best established genetic susceptibility marker has been identified in the alleles of the major histocompatability complex, a family of genes that play an important role in the immune system and autoimmunity. Specifically, the genetic risk factor for adults of northern European origins is localized to a form of the gene known as the HLA-DRB1 allele.  The researchers wanted to verify if this allele predicts MS in at-risk children with ADS.  Children, aged 16 or younger (266 children with ADS and 196 healthy controls) provided blood samples for genetic analysis.

    "What we found is that there is a higher frequency of HLA-DRB1 in children that would later be diagnosed with MS, but not in children presenting with a single episode of ADS. This indicates that this gene is a risk factor in paediatric-onset MS."  Children with ADS that do not go on to develop MS had no difference in HLA gene expression from controls indicating that the gene confers an increased risk for paediatric-onset MS, but not for acquired demyelination in general.

    This is one of several studies investigating paediatric MS as part of the CPDDN. As children with paediatric MS are closer to the early mechanisms and biology of the disease, they can also provide insights into factors that represent causes versus consequences of the disease.  One in 20 adults with MS can trace the disease back to a paediatric event, and therefore have had the disease for many years. This study reveals a fundamental similarity in genetic contribution to MS risk in both paediatric and adult-onset disease and underscores the importance of understanding the etiology of MS in children providing the possibility for earlier diagnoses and intervention and hopefully new therapies for MS.

    Source: (17/03/11)

    One-fifth of children with MS fail to respond to first-line treatment

    Disease Modifying DrugsResearchers from the National Network of Pediatric MS Centers of Excellence, in the first retrospective study of the response of children with multiple sclerosis to standard, or first-line, therapies, found that one-fifth of patients involved in the review required “second-line” treatments.

    Results of the study, published online first in the December 2010 issue of the Archives of Neurology, also reported that Hispanic children with MS were more likely to experience “break-through disease” while receiving first-line therapies than non-Hispanic children.

    E. Ann Yeh, UB assistant professor of neurology, is first author. In addition to UB, the National Network of Paediatric MS Centers includes Stony Brook University, University of California-San Francisco, University of Alabama-Birmingham, The Mayo Clinic and Massachusetts General Hospital.

    The review of data covering the records of 243 children treated an average of 3.9 years showed that 144 (58 percent) stayed on their first therapy, primarily interferon beta, 65 (25.2 percent) were switched to one other therapy, 29 (11.2 percent) were switched twice and 20 (7.8 percent) were switched three times.

    While most children switched to other first-line MS drugs, 55 children, or 21.3 percent had to be switched to a variety of “second-line” drugs, such as broad spectrum chemotherapies and corticosteroids, results showed. These children had shown MS relapses or new brain lesions detected on MRI scans.

    “Multiple papers on the use of first-line therapies in the paediatric MS population have been published over the past 10 years,” says Yeh, “and the use of first-line therapies in this population has come to be accepted as relatively safe. In practice, however, we were seeing more and more children who continued to have very active disease despite use of first-line therapies.

    “Little information on the use of second-line therapies in children with MS was available prior to the publication of this paper, so we set out to evaluate the use of second-line therapies in treatment-resistant cases of paediatric MS.”

    MS commonly is considered a disease diagnosed in young to middle-aged adults. However, studies have determined that 8,000-10,000 children in the U.S. have MS, which accounts for 2 to 5 percent of those diagnosed with the disease. As many as 10,000-15,000 children are estimated to experience MS symptoms.

    “The review clearly shows that a subset of children with paediatric MS has aggressive disease in need of chemotherapy or other second-line therapies,” says Yeh, “and, further, that these second-line therapies may be well tolerated in this group. It also suggests that almost 80 percent of children with MS will probably respond to one of the currently FDA-approved first-line MS therapies, such as interferons and glatiramer acetate.”

    Additional authors on the paper, all from the National Network of Pediatric MS Centers of Excellence, are Emmanuelle Waubant, Lauren B. Krupp, Jayne Ness, Tanuja Chitnis, Nancy Kuntz, Murali Ramanathan, Anita Bellman, Dorothee Chablas, Mark P. Gorman, Moses Rodriguez, John Robert Rinker II and Bianca Weinstock-Guttman.

    The research is supported by the National Multiple Sclerosis Society.

    Source: UB Reporter © 2011 University at Buffalo. (25/02/11)

    Cognitive impact of pediatric multiple sclerosis varies by race

    Paediatric Cognitive ImapirmentMultiple sclerosis (MS) affects some cognitive functions more severely in black children than white children, according to newly published research from an interdisciplinary team at the University of Alabama at Birmingham.

    The UAB researchers say the study, published in the Dec. 7, 2010, issue of Neurology, is the first to reveal that the severity of  cognitive difficulties in pediatric MS may vary between black and white children. The results provide valuable insight that could help individualize treatments for children suffering from the disease.

    "We don't yet understand the biological reasons, but the bottom line is treatment options must be re-evaluated and be aggressive enough, especially with black patients, to prolong quality of life for as long as possible," says Kelly Ross, M.A, a psychology doctoral degree candidate in the UAB College of Arts and Sciences and lead author of the study.

    MS is a chronic neurological disorder of the brain, spinal cord and optic nerves, which can cause subtle but debilitating impairments in learning and cognition and more apparent disruptions of motor control. Although MS in children is much less common than in adults, the disease may impact cognitive function more in younger patients because their nervous systems still are developing.

    The UAB team reviewed university-collected data on the cognitive assessments of 42 children with MS, 20 black and 22 white, who were treated from April 2006 to September 2009 at the UAB Center for Pediatric Onset Demyelinating Disorders, which operates at the Children's Hospital of Alabama.

    "The UAB CPODD clinic is the only one of the six Pediatric MS Centers of Excellence in the country that, based on its location, serves a considerable black population; this gave us access to unique comparative data," Ross says.

    Controlling for variables like socioeconomic status and education level, the researchers found that black MS patients may be at higher risk than whites for adverse cognitive impacts in the areas of language and complex attention, i.e. the ability to juggle multiple tasks at once.

    "The differential effects of the disease in children based on their race is a trend very similar to research in adults in which MS more severely affects some functions in black patients," says Jayne Ness, M.D., Ph.D., CPODD director and associate professor of pediatrics in the UAB School of Medicine and a co-author of the study.

    "Whether it is treatment of MS itself, adjunctive therapies or working with school systems to see that a proper special-education curriculum is in place, the results of this research could reshape the way we help pediatric MS patients and their families manage the disease," says Joe Ackerson, Ph.D., a former UAB faculty member and co-author of the study.

    In addition to Ross, Ness and Ackerson, David Schwebel, Ph.D., a professor of psychology, and John Rinker, M.D., an assistant professor of neurology, were co-authors of the study.

    Source: University of Alabama at Birmingham © 2008 University of Alabama at Birmingham (07/12/10)

    Low vitamin D levels increases risk of Paediatric MS

    Sunlight and Vitamin DLow serum vitamin D at the time of a first demyelinating event increases the risk of subsequent multiple sclerosis (MS) in children, according to a new study.

    Of 208 children under age 16 who experienced an acute demyelinating episode, 41 subsequently received a diagnosis of MS an average of eight months following their first symptom. Those with MS had an average serum vitamin D level of 52 nmol/L, versus 66 nmol/L for those remaining without an MS diagnosis, according to Heather Hanwell, MSc, a PhD candidate in the Department of Nutritional Science at the University of Toronto.

    The result extends the well-known connection between vitamin D and MS to pediatric MS cases, and, by placing deficiency so close to onset, strengthens the argument that vitamin deficiency plays a causal role in MS. The study was presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting.

    MS risk was also influenced by the HLA-DRB1*15 allele, previously shown to increase MS risk in adults, but there was no interaction detected between the gene and the vitamin, Hanwell said.

    The data came from a longitudinal study by the Canadian National Pediatric Demyelinating Diseases Network, a collaborative effort to understand pediatric multiple sclerosis and other demyelinating diseases.

    The network enrolls children who have developed an acquired demyelinating syndrome (ADS), "very similar to the CIS [clinically isolated syndrome] that we talk about in adults," Hanwell said. "At least a quarter of children with ADS go on to develop MS."

    "Several lines of evidence point to a window of susceptibility early in life," from the prenatal period to as late as age 15, she said, during which environmental risk factors may act to increase subsequent risk of MS. In this study, "we are able to capture factors at or near the time those factors are acting."

    The children in the study were enrolled from 23 sites across Canada. Blood samples were taken within 40 days of the demyelinating episode, and patients were followed regularly afterward for occurrence of a second episode and potential diagnosis of MS.

    While MS patients were older than non-MS patients, and older children have lower vitamin D levels, the difference in vitamin D levels between the groups remained significant even after correcting for age.

    Both groups had less vitamin D than they should, Hanwell noted. "Seventy-five nanomoles per liter is considered a conservative cutoff for vitamin D deficiency. These children are, on average, insufficient." One hundred nmol/L "is considered a possible therapeutic target for MS," she said.

    There was also a dose response. Those in the highest quartile, above 81 nmol/L, had one quarter of the risk of subsequent MS outcome, compared to those in the lowest quartile.

    The hazard ratio per nanomole was small, only 0.98, but, Hanwell said, "that 2% risk is actually quite meaningful," because it adds up. An increase of 10 nmol/L, for instance, would amount to a 20% risk reduction.

    Alberto Ascherio, MD, DrPH, of Harvard School of Public Health, commented, "I think this is interesting and important, because it is a look at vitamin D levels shortly after the acute episode. These data do support an effect from vitamin D, even though they are not fully prospective."

    "If vitamin D is, in fact, causal, it would be pretty dramatic, since over 80% of young adults have serum levels of under 100," he said. The risk of toxicity from supplementation is low, and the established benefits on other conditions are high. "Two hundred units per day would possibly be sufficient in most patients."

    Vitamin D can't explain everything in MS, he said. "But it is time to consider a very large randomized trial," involving hundreds of thousands of young people over several years, he suggested.

    Source: Medpage Today © 2004-2010 MedPage Today, LLC (16/10/10)

    Emerging concepts in pediatric-onset MS and related disorders

    MS MRIAbstract

    PURPOSE OF REVIEW: Pediatric-onset multiple sclerosis (MS) is increasingly recognized. Conversely, MS diagnosis in the pediatric population continues to be challenging, particularly in the youngest group of patients. An interesting amount of data has been recently published concerning immunopathogenesis, environmental factors, diagnosis, and treatment of MS in pediatric patients.

    RECENT FINDINGS: Recent studies have demonstrated that brain MRI criteria may distinguish MS from acute disseminated encephalomyelitis, and from nondemyelinating disorders in children. The presence of native myelin oligodendrocyte glycoprotein antibodies strongly correlates with a particular pediatric MS phenotype. Vitamin D, Epstein-Barr virus infection, and cigarette smoke are risk factors likely to act at specific stages during life. Diffuse tissue damage was confirmed in normal-appearing white matter at early stages of disease in children with MS, pointing to the need for early treatment interventions. The cognitive involvement of MS in children is progressive.

    SUMMARY: Pediatric-onset MS needs a prompt identification and early treatment. Further multinational research studies are still necessary to advance on genetic, immunologic, and imaging features on the initial and ongoing aspects of this disorder in the pediatric population.

    Tenembaum SN.

    Pediatric MS Clinic and Related Disorders, Department of Neurology, National Pediatric Hospital Dr J. P. Garrahan, Buenos Aires, Argentina.

    Curr Opin Pediatr. 2010 Sep 30. & Pubmed PMID: 20885330 (12/10/10)

    Juvenile Multiple Sclerosis associated with cognitive and psychosocial decline

    Paediatric MS & cognitive problemsYoung patients with multiple sclerosis (MS) face significant risks for cognitive impairment and psychiatric disorders as they get older, according to a prospective, 2-year follow-up study.

    "Our findings emphasize the importance of systematic assessment of cognitive and psychosocial issues to provide prompt management and counselling," write Maria Pia Amato, MD, from the Department of Neurology, University of Florence in Italy, and her colleagues from the Multiple Sclerosis Study Group of the Italian Neurological Society.

    "These findings point to further cognitive decline over time or decline from previously normal functioning occurring in the majority of the cases."

    The study reassessed 56 of an original 63 patients with childhood MS after a mean period of 2.1 years. At reassessment, patients ranged in age from 10.9 to 20.6 years, with a mean age of disease onset of 11.7 years.

    For the baseline study (Neurology. 2008;70:1891-1897), patients were compared to a group of healthy controls. These controls were no longer available at follow-up, and so a new group of 50 demographically matched controls was selected.

    The follow-up study assessed subjects with the same neuropsychological tests that had been used at baseline, administered in a single session of about 2 hours' duration.

    The study was published in the October 5 issue of Neurology.

    Deterioration in Language Skills Most Common

    The tests measured verbal learning and delayed recall (Selective Reminding Test), visuospatial learning (Spatial Recall Test), complex attention (Symbol Digit Modalities Test), planning (Tower of London Test), and expressive language (semantic, phonemic verbal fluency, and oral denomination tests from the Aachener Aphasic Test).

    Psychosocial features were measured using the Children's Depression Inventory, the Kiddie-SADS Present and Lifetime Version diagnostic interview, and the Fatigue Severity Scale.

    Parents were interviewed by a psychologist to gather information on school activities, hobbies, sports, and family and social relationships during the last year.

    Compared with the baseline evaluation, the patients' Expanded Disability Status Scale (EDSS) score had increased slightly, to 1.7.

    In addition, 70% were classified as being cognitively impaired (defined as failing at least 3 cognitive tests), compared with 31% at the baseline assessment. A further 22.6% exhibited minor cognitive dysfunction (failing 2 cognitive tests).

    In total, 75% of the patients had deteriorating cognitive function and 25% were classified as stable compared with baseline. The mean IQ of patients classified as cognitively impaired was lower than that of patients who were stable (90.3 vs 113.4).

    "Tests most frequently failed by cognitively impaired subjects tapped verbal learning and delayed recall, verbal fluency, verbal comprehension, and complex attention," write the study authors.

    "Deterioration in language skills confirms that the profile of deficits in this age range may be different compared to adult-onset cases, where linguistic abilities are usually observed," they add.

    Larger Proportion of Older Subjects Cognitively Impaired

    When the investigators compared subjects who were younger than 15 years with those who were older, they noticed a higher proportion of older subjects were cognitively impaired (70% vs 57%). In fact, older age was the only significant predictor of cognitive impairment (odds ratio, 1.9).

    Sex, disease duration, age of onset, cognitive impairment at baseline, EDSS score, relapse rate, IQ score, and depression and fatigue scores were not predictive of deteriorating cognitive performance.

    Psychiatric disorders were documented in 47% of subjects. Depressive symptoms were recorded in 17% of subjects compared with 6% at baseline, based on the Children Depression Inventory.

    In addition, among 39 subjects in which the Kiddie-SADS Psychiatric Interview was obtained, there were 12 (30.5%) with psychiatric disorders, including major depression (n = 6), depression and anxiety (n = 2), panic disorders (n = 2), and bipolar disorder (n = 2).

    "The frequent occurrence of psychiatric problems in this age range clearly deserves further research and calls for regular screening and treatment in clinical practice," they write.

    A total of 11 patients (21%) were classified with fatigue.

    Interviews with parents revealed that school activities were negatively affected in 28% of subjects. At least 30 school days had been missed by 90% of subjects due to medical appointments, relapses, and adverse effects.

    Hobbies and sports were negatively affected in 41% of subjects, and 28% reported family and social relationships were negatively affected.

    Young MS Patients Particularly Vulnerable

    Children and adolescents with MS may be "particularly vulnerable to cognitive problems because the neuropathologic processes of the disease occur during primary central nervous system myelination and can produce both white matter and gray matter changes," the study authors write.

    They hypothesized that MS patients aged 15 years or more, "who are in a critical phase for development of cognitive and academic competences, are more likely to show a gap in cognitive test performance when compared with healthy peers who in the same period are attaining cognitive abilities at a very fast rate. Hopefully, this gap might be mitigated over time due to compensatory and therapeutic strategies."

    They noted that higher inflammatory activity documented in the group older than 15 years, compared with adults, might further explain their cognitive worsening.

    Finally, they suggested that earlier treatment of all ages after disease onset might positively influence cognition. "Although most of our patients were under treatment, only 14 subjects were treated within 1 year from disease onset."

    The study provides "an important additional dimension to our understanding of children with MS," commented Lauren B. Krupp, MD, from the National Pediatric Multiple Sclerosis Center at Stony Brook University Medical Center in New York, and Ralph H. B. Benedict, PhD, from Jacobs Neurological Institute, State University of New York at Buffalo, in an accompanying editorial

    "Earlier identification of the deficits is critical, so that special accommodations can be implemented, such as longer times for test taking. Whether early initiation of MS therapies can help delay the cognitive decline remains unclear and should be addressed by future research."

    Dr. Amato has served on scientific advisory boards for Biogen Idec, Bayer Schering Pharma, and Sanofi-Aventis, and receives research support and speaker honoraria from Biogen Idec, Merck Serono, Bayer Schering Pharma, and Sanofi-Aventis. Full disclosures for the other investigators can be found in the original article.

    Neurology. 2010;75:1134-1140, 1128-1129.

    Source: Medscape Today Copyright © 1994-2010 by WebMD LLC.(07/10/10)

    Safety and efficacy of natalizumab in children with multiple sclerosis

    OBJECTIVE: To describe the effect of natalizumab in the treatment of subjects with active multiple sclerosis (MS) treated before the age of 18 years.

    METHODS: Nineteen paediatric subjects with MS (mean age 14.6 +/- 2.2 years, mean number of attacks 5.2 +/- 1.9 during the pretreatment phase of 27.7 +/- 19.7 months, median pretreatment Expanded Disability Status Scale score [EDSS] 2.5, range 1.0-5.0) were treated with natalizumab at the dose of 300 mg every 28 days. After treatment initiation, patients were reassessed clinically every month; brain MRI was performed at baseline and every 6 months.

    RESULTS: Patients received a median number of 15 infusions (range 6-26). A transient reversible worsening of preexisting symptoms occurred in 1 subject during and following the first infusion. All the patients remained relapse-free during the whole follow-up. The median EDSS decreased from 2.5 to 2.0 at the last visit (p < 0.001). EDSS remained stable in 5 cases, decreased by at least 0.5 point in 6 cases, and decreased by at least 1 point in 8 cases. At baseline, the mean number of gadolinium-enhancing lesions was 4.1 (range 1-20). During the follow-up, no gadolinium-enhancing lesions were detected (p = 0.008); 3 patients developed new T2-visible lesions at month 6 scan but the overall number of T2 lesions remained stable during the subsequent follow-up. Transient and mild side effects occurred in 8 patients.

    CONCLUSIONS: Natalizumab was well-tolerated in all subjects. A strong suppression of disease activity was observed in all subjects during the follow-up. Classification of evidence: This study provides Class IV evidence that natalizumab, 300 mg IV once every 28 days, decreased EDSS scores in paediatric patients with MS over a mean treatment period of 15.2 months.

    Ghezzi A, Pozzilli C, Grimaldi LM, Brescia Morra V, Bortolon F, Capra R, Filippi M, Moiola L, Rocca MA, Rottoli M, Sarchielli P, Zaffaroni M, Comi G.

    Centro Studi Sclerosi Multipla, Via Pastori 4, Ospedale di Gallarate, Gallarate, Italy.

    Source: Neurology. 2010 Sep 7;75(10):912-7 & Pubmed PMID: 20820002

    Executive functioning in children & adolescents with Multiple Sclerosis

    Adolescent MS Cognition ProblemsSummary
    Executive Functions (EF) include a range of superordinate abilities that control performance across many tasks allowing for cognitive efficiency and mental flexibility.

    Although EFs are commonly affected in MS, little is known about the EF components that are most affected, particularly in paediatric-onset MS patients.

    The objective of this work was to evaluate the components of executive function (EF) that are impaired in paediatric multiple sclerosis (MS), and determine the clinical and neural correlates of impaired EF.

    Participants included 32 MS patients (26 females) and 20 controls (17 females) group-matched for sex and age, with a mean age at assessment of 16.2 ±2.1 years for patients and 15.5 ±1.9 years for controls.

    EF components measured were attentional control / working memory, inhibition, cognitive flexibility, information processing, and behavioural manifestation of EF (as measured by parent-report on the BRIEF).

    Multiple linear regression analyses were performed to assess the correlation of impaired EF components with clinical (age of disease onset, disease duration, and total number of relapses) and neuroimaging (T1- and T2- weighted total brain lesion volume (LV), and T2 frontal lobe LV) variables, adjusting for age, sex, and IQ.

    Lesions were segmented using a fully automated, multi-spectral Bayesian technique, with manual correction where necessary.
    Patients had a mean age of disease onset of 12.1 ± 3.7 years, average disease duration of 4.1  ± 3.2 years, and an average of 3.3  ± 2.1 relapses.

    Relative to controls, MS patients had significantly lower IQ (t=-3.63, p<.01), and performed significantly poorer on measures of information processing and cognitive flexibility.

    In MS patients, T2-weighted total brain and frontal lobe LV were significantly associated with all measures of EF, with adjusted r2 values ranging from 0.43 to 0.46 (p<.01 for all).

    CONCLUSIONS / RELEVANCE: EF abilities are significantly reduced in paediatric MS patients compared with controls.

    Reductions in EF correlate with total brain and frontal lobe LV, which highlights the impact of inflammatory activity on MS-related executive dysfunction.

    Ameeta Dudani, North York, ON, Canada, Rezwan Ghassemi, Sridar Narayanan, Douglas Arnold, Montreal, QC, Canada, John Sled, Brenda Banwell, Christine Till, Toronto, ON, Canada AAN Toronto 2010 [IN2-1.003]

    Supported by: The Canadian Institutes of Health Research (CIHR), The Multiple Sclerosis (MS) Society of Canada, and The Canadian MS Scientific Research Foundation.              

    Source: The Multiple Sclerosis (MS) Society of Canada (30/07/10)

    Cognitive rehabilitation in children and adolescents with multiple sclerosis

    Paediatric MS Cognitive ProblemsAbstract 
    Cognitive impairment can be detected in a sizeable proportion of paediatric multiple sclerosis (MS) patients. It involves memory, complex attention, information processing speed, executive functions, linguistic abilities, and intelligent quotient. It has a great impact on school, everyday and social activities, and significantly progresses overtime in the great majority of the subjects.

    These findings highlight the importance of a comprehensive and systematic assessment of MS-related cognitive difficulties in paediatric cases. Moreover, despite the acknowledged relevance of cognitive impairment in this age range, specific interventions for paediatric MS are lacking.

    As for rehabilitative strategies, there is some evidence of efficacy in other diseases, in particular brain trauma, tumor, and stroke. The development of effective rehabilitative strategies tailored to the needs of young MS patients is a priority for future research in the field.

    Emilio Portaccio1 , Benedetta Goretti1, Valentina Zipoli1, Bahia Hakiki1, Marta Giannini1, Luisa Pastò1, Lorenzo Razzolini1 and Maria Pia Amato1

    (1) Department of Neurology, University of Florence, Viale Morgagni, 85, 50134 Florence, Italy

    Source: SpringerLink Milan © Springer 2010 (22/07/10)

    MS & solar exposure before the age of 15 years

    Sunshine & MSAbstract
    Few studies report a protective role of childhood solar exposure to multiple sclerosis.

    Our objective was to confirm the protective role of childhood solar exposure in multiple sclerosis in Cuba, Martinique and Sicily.

    This was a matched case-control study, and cases met Poser criteria for clinically, laboratory (definite, probable) multiple sclerosis.

    Controls were resident population, without neurological disorder, living close to cases (within 100 km), matched for sex, age (+/-5 years), residence before age 15. We recruited 551 subjects during a 1-year period (193 cases, Cuba n = 95, Sicily n = 50, Martinique n = 48; 358 controls). Some (89%) met definite clinical multiple sclerosis criteria (relapsing-remitting form (with and without sequel) (74%), secondary progressive (21%), primary progressive (5%)).

    Odds ratios in a univariate analysis were: family history of multiple sclerosis (5.1) and autoimmune disorder (4.0); wearing shirt (3.5), hat (2.7), pants (2.4); sun exposure causing sunburn (1.8); sun exposure duration (1 h more/day; weekends 0.91, weekdays 0.86); bare-chested (0.6); water sports (0.2).

    Independent factors in the multivariate analysis were family history of multiple sclerosis (4.8 (1.50-15.10)), wearing pants under sunlight (1.9 (1.10-3.20)), sun exposure duration (1 h more/day, weekdays 0.90 (0.85-0.98), weekends 0.93 (0.87-0.99)), water sports (0.23 (0.13-0.40)).

    We conclude that outdoor leisure activities in addition to sun exposure reports are associated with a reduced multiple sclerosis risk, with evidence of dose response.

    Dalmay F, Bhalla D, Nicoletti A, Cabrera-Gomez J, Cabre P, Ruiz F, Druet-Cabanac M, Dumas M, Preux P.

    Université de Limoges, IFR 145 GEIST, Institut de Neurologie Tropicale; EA 3174 NeuroEpidémiologie Tropicale et Comparée, Faculté de Médecine, Limoges, France

    Source: Pubmed PMID: 20463038 (19/05/10)

    Psychosocial issue in children and adolescents with MS

    Paediatric MS Psychosocial IssuesAbstract
    In adult-onset multiple sclerosis (MS) cases, major depression, fatigue and psychological distress are common, whereas there is little information on these issues in children with the disease.

    The aim of this study was to assess psychosocial disorders in an Italian cohort of children and adolescent with MS.

    We evaluated 56 patients through self-assessment scales of depression (Children Depression Inventory) and fatigue (Fatigue Severity Scale), a psychiatric interview [Kiddie-SADS-Present and Lifetime Version (K-SADS-PL)] and an interview on school and everyday activities.

    Significant fatigue was found in 11 patients (20%). Twelve of the 39 patients who underwent the K-SADS-PL received a formal diagnosis of an affective disorder. Moreover, MS affected school activities in 28% of cases, daily living activities in 41% and social relationships in 28%.

    Our study confirms the critical role of psychosocial difficulties in children and adolescents with MS and provides a few cues to clinical management.

    Goretti B, Ghezzi A, Portaccio E, Lori S, Zipoli V, Razzolini L, Moiola L, Falautano M, De Caro MF, Viterbo R, Patti F, Vecchio R, Pozzilli C, Bianchi V, Roscio M, Comi G, Trojano M, Amato MP.

    Department of Neurology, University of Florence, Florence, Italy

    Source: Pubmed PMID: 20454820 (19/05/10)

    Vitamin D status is associated with relapse rate in paediatric-onset multiple sclerosis

    Vitamin DAbstract
    We sought to determine if vitamin D status, a risk factor for multiple sclerosis, is associated with the rate of subsequent clinical relapses in paediatric-onset multiple sclerosis.

    METHODS: This is a retrospective study of patients with paediatric-onset multiple sclerosis or clinically isolated syndrome who were consecutively recruited into a prospective cohort at their clinical visit at the paediatric multiple sclerosis center of University of California, San Francisco or State University of New York at Stony Brook.

    Of 171 eligible patients, 134 (78%) with multiple sclerosis/clinically isolated syndrome were included in the cohort; a further 24 were excluded from this analysis due to lack of available serum (n = 7) or lack of follow-up (n = 17). Serum 25-hydroxyvitamin D(3) levels were measured and were adjusted to reflect a deseasonalized value. The adjusted serum 25-hydroxyvitamin D(3) level was the primary predictor in a multivariate negative binomial regression model in which the main outcome measure was the number of subsequent relapses.

    RESULTS: Among the 110 subjects, the mean unadjusted 25-hydroxyvitamin D(3) level was 22 +/- 9 ng/ml. After adjustment for age, gender, race, ethnicity, disease duration, disease-modifying therapy, and length of follow-up, every 10 ng/ml increase in the adjusted 25-hydroxyvitamin D(3) level was associated with a 34% decrease in the rate of subsequent relapses (incidence rate ratio, 0.66; 95% confidence interval, 0.46-0.95; p = 0.024).

    INTERPRETATION: Lower serum 25-hydroxyvitamin D(3) levels are associated with a substantially increased subsequent relapse rate in paediatric-onset multiple sclerosis or clinically isolated syndrome, providing rationale for a randomized controlled trial of vitamin D supplementation.

    Mowry EM, Krupp LB, Milazzo M, Chabas D, Strober JB, Belman AL, McDonald JC, Oksenberg JR, Bacchetti P, Waubant E.

    MS Center, Department of Neurology, University of California, San Francisco, San Francisco, CA 94117, USA.

    Source: Pubmed PMID: 20437559 (05/05/10)

    A comparison of MRI criteria for diagnosing paediatric ADEM and MS

    MRIBACKGROUND: Brain MRI is a useful tool for diagnosing inflammatory demyelinating disorders in children. However, it remains unclear which are the most reliable criteria for distinguishing multiple sclerosis (MS) from monophasic disorders such as acute disseminated encephalomyelitis (ADEM). We therefore compared the 4 current sets of MRI criteria in our Dutch paediatric cohort and determined which are the most useful in clinical practice for distinguishing ADEM from MS.

    METHODS: We included 49 children who had had a demyelinating event and an MRI scan within 2 months of their first clinical attack. Twenty-one patients had ADEM and remained relapse-free after at least 2 years of follow-up. Twenty-eight patients had a definitive diagnosis of MS. We assessed the sensitivity and specificity of the following MRI criteria: Barkhof criteria, KIDMUS criteria, Callen MS-ADEM criteria, and Callen diagnostic MS criteria.

    RESULTS: The Callen MS-ADEM criteria had the best combination of sensitivity (75%) and specificity (95%). The KIDMUS criteria had higher specificity (100%), but much lower sensitivity (11%). The Barkhof criteria had a sensitivity of 61% and a specificity of 91%. The Callen diagnostic MS criteria were the most sensitive (82%), but were only 52% specific for distinguishing a first attack of MS from ADEM.

    CONCLUSIONS: The results in our cohort demonstrate that the new Callen criteria for multiple sclerosis-acute disseminated encephalomyelitis (MS-ADEM) are the most useful for differentiating a first attack of MS from monophasic ADEM. Although the Callen diagnostic MS criteria are more sensitive, they lack the specificity necessary to differentiate MS from ADEM.

    Ketelslegers IA, Neuteboom RF, Boon M, Catsman-Berrevoets CE, Hintzen RQ; On behalf of the Dutch Pediatric MS Study Group.

    From the Department of Neurology (I.A.K., R.F.N., R.Q.H.), Erasmus MC University Medical Center, Rotterdam; Department of Pediatric Neurology (M.B.), University Medical Center Groningen, Groningen; and Department of Pediatric Neurology (C.E.C.-B.), Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands.

    Source: PubMed PMID: 20335562 (31/03/10)

    Drinking milk during pregnancy lowers risk of multiple sclerosis in children

    MilkDrinking milk during pregnancy reduces the chances of development of multiple sclerosis in children in their later life, says a new research study presented at the American Academy of Neurology’s annual meeting in Toronto, Canada.

    The researchers from the Harvard School of Public Health in Boston, US found that children born to pregnant mothers who drank milk were at lower risk of having multiple sclerosis. This was similar in cases where the mothers took vitamin D during pregnancy as well.

    Multiple sclerosis is a medical condition where the brain nerves are damaged and fails to communicate with the spinal cord. It may be seen relapsing in some cases and also show accumulation of the myelin sheaths over time. The common symptoms of this disease are weakness in muscles, spasms and difficulty in movement.

    A study of 35,794 female nurses whose their mothers provided information about their diet pattern during pregnancy established the link between multiple sclerosis and pregnancy. Out of those nurses who took part in the study, 199 were found to develop multiple sclerosis after a span of 16 years.

    The risk of multiple sclerosis was seen to be lower by 56 percent in daughters whose mothers drank milk (four glasses everyday) during pregnancy compared to those mothers who drank less than three glasses.

    The mothers who consumed vitamin D during pregnancy gave birth to daughters with 45 percent lower risk than those whose vitamin D intake was less.

    The findings of the study can help the mothers start having vitamin D and more milk during pregnancy to avoid their children suffer from multiple sclerosis when they grow up.

    Source: Bolo Health © 2009 (10/02/10)

    Low Vitamin D levels are associated with greater risk of MS relapse

    Vitamin DLow vitamin D blood levels are associated with a significantly higher risk of relapse attacks in patients with multiple sclerosis (MS) who develop the disease during childhood, according to a study conducted by researchers from the University of California, San Francisco.

    “We have known for some time that vitamin D insufficiency is a risk factor for developing MS, but this is the first study to assess whether vitamin D levels influence the disease course of those who already have MS,” said lead author Ellen Mowry, MD, MCR, a clinical instructor of neurology at the UCSF Multiple Sclerosis Center.

    The study, which is now published online by the “Annals of Neurology” and is available at , demonstrates that an increase in vitamin D levels by 10 nanograms per milliliter of blood (ng/mL) corresponds with a 34 percent decrease in the rate of subsequent relapses.

    In other words, raising the vitamin D level of a person with MS by 15 ng/mL, which requires about 2,000 international units of vitamin D supplementation a day, could theoretically cut a patient’s relapse rate in half, explained Mowry.

    “Although we do not yet know if vitamin D supplementation will be beneficial for MS patients, the fact that there is a clear association between vitamin D levels and relapse rate provides strong rationale for conducting a clinical trial to measure the potential impact of supplementation,” she said.

    “This is an exciting finding because it indicates that it is very possible for vitamin D supplementation to have a profound impact on the course of this disease,” said senior author Emmanuelle Waubant, MD, PhD, an associate professor of neurology at UCSF and director of the Regional Pediatric MS Center at UCSF Children’s Hospital. Waubant said she expects similar findings in adult patients with MS.

    Multiple sclerosis is a chronic and often disabling disease that affects the central nervous system, which comprises the brain, spinal cord and optic nerves. A type of autoimmune disorder, MS causes the body’s own defense system to break down a substance called myelin, which surrounds and protects nerve fibers.

    Although MS occurs most commonly in adults, a small proportion of cases are diagnosed in children and adolescents. According to the National MS Society, two to five percent of all people with MS experience their first symptoms before the age of 18.

    The researchers measured vitamin D levels through blood samples from 110 patients whose MS symptoms began at age 18 or younger. The patients were seen at either UCSF Children’s Hospital or the State University of New York Stony Brook’s Regional Pediatric MS Center of Excellence – two of six multidisciplinary referral centers in the United States sponsored by the National MS Society.

    After providing the initial blood sample, patients were followed for an average of 1.7 years, during which the researchers recorded the total number of relapses each patient experienced. According to Mowry, a relapse or flare-up of MS causes new neurologic symptoms or the worsening of old ones, such as impaired vision, problems with balance, or numbness. Relapses can be very mild or severe enough to interfere with a person’s ability to function.

    During the follow-up period, the researchers assessed the patients’ relapse rates and vitamin D levels after controlling for such factors as age, gender, race, ethnicity, use of MS treatments and the duration of follow-up care.

    “If we are able to confirm that vitamin D supplementation is an effective treatment, my hope is that it will help improve the quality of life for all MS patients,” Mowry said.

    In addition to a randomized clinical trial of vitamin D supplementation in MS patients, Mowry said further studies are also needed to determine the mechanism by which vitamin D affects inflammatory processes and, in turn, eases symptoms of MS.

    Additional co-authors from UCSF include Dorothee Chabas, MD, PhD; Jonathan Strober, MD; Jamie McDonald, BS; Jorge Oksenberg, PhD, and Peter Bacchetti, PhD. Co-authors from other institutions are Lauren Krupp, MD; Maria Milazzo, MS, CPNP, and Anita Belman, MD, all of the Pediatric MS Center, State University of New York at Stony Brook.

    The study was supported by a National MS Society Sylvia Lawry Fellowship Award and an additional grant from the National MS Society.

    Source: PRWEB (21/01/10)

    Fatigue and quality of life in paediatric Multiple Sclerosis

    Fatigue in Paediatric MS Fatigue and quality of life are significant concerns in adult multiple sclerosis (MS) but little is known about these factors in paediatric MS.

    The present investigation evaluates fatigue and quality of life in 51 paediatric MS patients to determine the rate of fatigue and reduced quality of life and assesses the relations between these variables and clinical factors.

    Fatigue and quality of life were assessed by self- and parent-report via the PedsQL Multidimensional Fatigue Scale and the PedsQL Quality of Life Scale.

    One-sample t-tests determined if scores were below published data for healthy individuals. Moreover, scores falling one standard deviation from norms were considered mildly affected, with severe difficulties being defined as scores falling two or more standard deviations from norms.

    Associations between self- and parent-reported difficulties and clinical factors were examined via Pearson correlation analyses.

    In comparison with healthy samples, paediatric MS patients reported greater difficulties with respect to fatigue, sleep, cognition, physical limitations, and academics. In addition to significant difficulties on these factors, parents reported problems with respect to emotional functioning, and tended to report greater fatigue, sleep, and cognitive difficulties than were self-reported.

    Expanded Disability Status Scale score was the only neurologic variable significantly related to fatigue or quality of life scores. Fatigue was significantly correlated with reports of sleep difficulties, cognitive problems, and quality of life variables. These findings suggest that fatigue and poorer quality of life is a clear concern in paediatric MS, and is related to overall physical disability.

    Macallister WS, Christodoulou C, Troxell R, Milazzo M, Block P, Preston TE, Bender HA, Belman A, Krupp LB.

    New York University.

    Source: Pubmed PMID: 19965517 (17/12/09)

    MS is more aggressive in children but slower to cause disability than in adults

    MS MRIMagnetic resonance images (MRI) of patients diagnosed with multiple sclerosis in childhood show that pediatric onset multiple sclerosis is more aggressive, and causes more brain lesions, than MS diagnosed in adulthood, researchers at the University at Buffalo have reported.

    Interestingly, however, patients with pediatric-onset MS -- which comprise up to 5 percent of total MS cases -- develop disabilities at a slower pace than patients with adult-onset MS, the data showed.

    "Patients with pediatric-onset MS have three times as many relapses annually than patients with adult-onset disease, which suggests there is greater disease activity in this population," said Bianca Weinstock-Guttman, MD, associate professor of neurology in the UB School of Medicine and Biomedical Sciences and corresponding author.

    "But surprisingly, the average time to reach the secondary progressive phase of the disease is longer in patients who develop MS in childhood than in adult onset MS," she continued. "Reaching the next stage of disability is almost 10 years longer in pediatric-onset patients."

    Commenting on the study, Helen Yates, Multiple Sclerosis Resource Centre Chief Executive said, “This research is very interesting and has produced a somewhat unexpected result.  It has long been believed that relapse rate has a direct correlation to the increased rate of disability but this work suggests that this is not necessarily the case when it comes to MS diagnosed in childhood.  Obviously there needs to be more follow up research on this specific area to gain further insight into childhood MS”

    Weinstock-Guttman directs the Pediatric Multiple Sclerosis Center of Excellence located at Women and Children's Hospital, and the William C. Baird MS Center in Buffalo General Hospital (BGH), both Kaleida Health affiliates and UB teaching hospitals.

    Eluen A. Yeh, MD, UB assistant professor of neurology and co-director in the Pediatric Multiple Sclerosis Center, is first author on the study, which was published online Nov. 5 in Brain.

    The National Multiple Sclerosis Society estimates that 8,000 to 10,000 children (defined as up to 18 years old) in the U.S. have multiple sclerosis, and another 10,000 to 15,000 have experienced at least one symptom suggestive of MS. The disease causes demyelination -- destruction of the sheath that protects and insulates nerve fibers. Breaks in the myelin sheath disrupt the flow of electrical impulses, causing loss of sensation and coordination.

    The UB study involved four sets of patients:

    • 17 children with an average age of 13.7 who were diagnosed with MS 2.7 years earlier

    • 33 adults with an average age of 36.5 years who were diagnosed with pediatric MS 20 years earlier

    • 81 adults with an average age of 40 who have had MS for an average of 2.6 years

    • 300 adults with an average age of 50.5 who've had MS for 20 years

    All participants underwent a brain MRI scan at facilities at BGH and at Women and Children's Hospital, while the specific MRI metric analysis was performed at the Buffalo Neuroimaging Analysis Center (BNAC), part of the UB Department of Neurology/Jacobs Neurological Institute, located in BGH. Robert Zivadinov, MD, PhD, UB associate professor of neurology, is director of the BNAC.

    The MRI measured two types of brain tissue damage: T1-lesion volume, which shows "black holes," or hypointense lesions, which are areas of permanent axonal damage; and T2-lesion volume, which shows the total number of lesions (lesion load) and overall disease burden.

    Both of these measures indicated that MS is more aggressive in children in the early stages, said Yeh.

    "This corresponds with recent data that suggest a higher lesion burden in pediatric MS than adult-onset MS. These findings are somewhat surprising, considering we have assumed that children generally have a greater capacity for central nervous tissue repair."

    "Our findings, which are limited to a cross-sectional study design, suggest that children have a somewhat better reserve and functional adaptability than adults, but less support for a better remyelination process," added Weinstock-Guttman. "However, the remyelination process may require a more in-depth prospective analysis"

    Weinstock-Guttman said the data support the need for early diagnosis and therapeutic intervention in pediatric MS patients.

    Murali Ramanathan, PhD, associate professor in the departments of Pharmaceutical Sciences and Neurology in the UB School of Pharmacy and Pharmaceutical Sciences and School of Medicine and Biomedical Sciences, respectively, also contributed significantly to the research. Additional contributors were Jennifer L. Cox, PhD, research assistant professor and BNAC's director of neuroimaging, and neurology research assistants Deepa Preeti Ramasamy and Laura M. Willis.

    The research was supported in part by grants from the National Multiple Sclerosis Society and Children's Guild Foundation of Buffalo.

    Source: Insciences Organisation Copyright Insciences Organisation 2009 and MSRC(17/11/09)

    Difference in disease burden and activity in pediatric patients on brain magnetic resonance imaging at time of Multiple Sclerosis onset vs adults

    MS MRI

    Objective:  To compare initial brain magnetic resonance imaging (MRI) characteristics of children and adults at multiple sclerosis (MS) onset.

    Design:  Retrospective analysis of features of first brain MRI available at MS onset in patients with pediatric-onset and adult-onset MS.

    Setting:  A pediatric and an adult MS center.

    Patients:  Patients with pediatric-onset <18 years) and adult-onset (18 years) MS.

    Main Outcome Measures:  We evaluated initial and second (when available) brain MRI scans obtained at the time of first MS symptoms for lesions that were T2-bright, ovoid and well defined, large (1cm), or enhancing.

    Results:  We identified 41 patients with pediatric-onset MS and 35 patients with adult-onset MS. Children had a higher number of total T2- (median, 21 vs 6; P < .001) and large T2-bright areas (median, 4 vs 0; P < .001) than adults. Children more frequently had T2-bright foci in the posterior fossa (68.3% vs 31.4%; P = .001) and enhancing lesions (68.4% vs 21.2%; P < .001) than adults. On the second brain MRI, children had more new T2-bright (median, 2.5 vs 0; P < .001) and gadolinium-enhancing foci (P < .001) than adults. Except for corpus callosum involvement, race/ethnicity was not strongly associated with disease burden or lesion location on the first scan, although other associations cannot be excluded because of the width of the confidence intervals.

    Conclusion:  While it is unknown whether the higher disease burden, posterior fossa involvement, and rate of new lesions in pediatric-onset MS are explained by age alone, these characteristics have been associated with worse disability progression in adults.

    Authors: Emmanuelle Waubant, MD, PhD; Dorothee Chabas, MD, PhD; Darin T. Okuda, MD, MSc; Orit Glenn, MD; Ellen Mowry, MD; Roland G. Henry, PhD; Jonathan B. Strober, MD; Bruno Soares, MD; Max Wintermark, MD; Daniel Pelletier, MD

    Author Affiliations: UCSF Regional Pediatric Multiple Sclerosis Center (Drs Waubant, Chabas, and Strober), UCSF Adult Multiple Sclerosis Center (Drs Okuda, Mowry, and Pelletier), and Department of Radiology, University of California, San Francisco (Drs Glenn, Henry, Soares, and Wintermark).

    Source: Arch Neurol. 2009;66(8):967-971. (11/08/09)

    New studies show Vitamin D deficiency could cause Multiple Sclerosis in children

    Vitamin D

    Children who develop multiple sclerosis have substantially lower levels of vitamin D than children who do not develop the disease, according to a series of studies presented at an international conference on multiple sclerosis in Montreal.

    Multiple sclerosis is a degenerative disease of the nervous system in which the myelin sheath that insulates nerve cells breaks down, leading to problems in the transmission of nervous signals. Symptoms can range from tingling and numbness to tremors, paralysis or blindness. An estimated 2.5 million people around the world suffer from the disease, which is rarely diagnosed before the age of 15.

    In one study, researchers from the University of Toronto tested the vitamin D blood levels of 125 children who had exhibited symptoms indicating some form of damage to the myelin sheath.

    "Three-quarters of our subjects were below the optimal levels for vitamin D," lead researcher Heather Hanwell said.

    After a year, the researchers compared the data from the 20 children who had since been diagnosed with multiple sclerosis with those who had not exhibited any further demyelinating symptoms. They found that the average vitamin D levels of children who had been diagnosed with multiple sclerosis were substantially lower than those of the other children. Among the diagnosed children, 68 percent of children were actually deficient in the vitamin.

    A similar study was conducted by researchers from Toronto's Hospital for Sick Children.

    "Seventeen of 19 children who had been diagnosed with MS had vitamin D levels below the target level," researcher Brenda Banwell said.

    Researchers have suspected a connection between vitamin D and multiple sclerosis for many years, ever since discovering that the disease is more common at more northern latitudes. Because the body synthesizes vitamin D upon exposure to sunlight, deficiency is much more common in places where the sun is weaker, especially during the winter.

    "There is a very consistent pattern of latitude and multiple sclerosis," said epidemiologist and multiple sclerosis researcher Cedric Garland of the University of California-San Diego.

    Hanwell directly linked Canada's northern latitude to its high rates of multiple sclerosis.

    "In Canada for six months of the year the sun is not intense enough for us to manufacture vitamin D in our skin," she said.

    Canada has one of the highest multiple sclerosis rates in the world. One of the few countries with a higher rate is Scotland, which has regions reached by only a quarter of all available sunlight. Recent research has confirmed a strong connection in Scotland between vitamin D deficiency and poor health status.

    "People have been looking for things in the environment that might account for why Canada has such a high MS risk, and this is one of those factors," Banwell said.

    It remains unclear exactly how vitamin D might influence multiple sclerosis risk, but researchers believe it may have to do with the immune system. New research continues to illuminate the role that vitamin D plays in the immune system, providing protection against cancer, tuberculosis and autoimmune diseases.

    Many health researchers believe that multiple sclerosis is an autoimmune disease.

    "Vitamin D acts as an immune modulator," Banwell said. "On our immune cells there are what are known as receptors, a docking mechanism, for vitamin D. In MS, there are many lines of evidence that immune cells are not regulated properly."

    Researchers called vitamin D research one of the most promising areas of research into causes and potential cures for multiple sclerosis.

    "The Canadian findings are very exciting and raise the possibility of targeting children at risk of MS and preventing some of the disease," said vitamin D researcher Oliver Gillie.

    To prove that vitamin D is effective as a multiple sclerosis treatment or preventive - as well as to figure out what dose would be needed - researchers would first have to conduct large-scale clinical trials.

    Source: Natural © 2009 Natural News Network. All Rights Reserved (08/06/09)

    Paediatric Multiple Sclerosis discovery could lead to new disease diagnostics

    MS Proteins

    A group of 12 proteins associated with pediatric multiple sclerosis (MS) have been discovered for the first time by a team of neurology and pathology researchers at Stony Brook University Medical Center. Led by Lauren Krupp, M.D., Director of the National Pediatric MS Center at SBUMC, the finding could lead to a new panel of diagnostic and prognostic markers in paediatric MS. Their study is reported in the April 2009 issue of the journal Multiple Sclerosis.

    Multiple Sclerosis is an inflammatory autoimmune disease of the central nervous system (CNS) which usually affects young adults. It is the most disabling chronic disorder of this age group, affecting more than 400,000 in the United States. In some instances, children can be affected. Diagnosing MS in children and adolescents is difficult, and standard MS diagnostic tests such as cerebral spinal fluid (CSF) analysis and magnetic resonance imaging (MRI) are often unreliable.

    “This is the first study of its kind in children with MS that has the potential to advance progress in the diagnosis and estimation of the prognosis of all individuals affected by this disease,” says Dr. Krupp, noting the potential of the method as an early disease-specific marker.

    The Stony Brook team used specialized techniques for measuring multiple proteins at once (a method known as proteomics) in the blood of children with MS. They used plasma samples from nine children with MS and plasma from nine healthy children to complete the proteomic analysis. The researchers found differences in the amounts of multiple proteins in the blood of children with MS compared to those without disease. They found 12 proteins that differed in expression in the MS group. Some of the proteins had not been previously associated with disease.

    “Proteomics is just being applied to the study of MS,” explains Dr. Krupp. “Because children develop MS so early with respect to potential environmental exposures, it is possible that determining the mechanism of action in MS of the identified proteins will elucidate further the pathogenesis of the disease.”

    In “Protein expression profiles in pediatric multiple sclerosis: potential biomarkers,” the authors detail the proteomic analysis method. They used two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry to identify the proteins that were significantly expressed in pediatric MS group. This analysis was completed through the Proteomics Center at Stony Brook University.

    The study was limited to children who met the international consensus definition of paediatric MS. All nine MS patients were girls age 14 to 17 years. They were matched to controls of healthy girls within the same age range.

    According to the researchers, a larger number of subjects are needed to further validate their study findings. They believe their findings provide a significant basis for large studies to confirm and validate biomarker suitability in the blood. They will pursue such studies with the ultimate aim of identifying MS biomarkers that lead to the development of rapid, easy-to-use, widely available, and inexpensive MS diagnostic tests.

    The Stony Brook pediatric MS proteomic research was supported, in part, with funding to Dr. Krupp from the Montel Williams MS Foundation and the National Multiple Sclerosis Society grant to the National Pediatric MS Center and National Center for Research Resources. Co-investigator Noy Rithidech, Ph.D., of the Department of Pathology, also received grants to complete the research from the Office of the Vice President for Research and the Office of Scientific Affairs at Stony Brook University, and NASA.

    Source: Newswire Medical News © 2009 Newswise.(22/04/09)

    Birmingham heads major study into multiple sclerosis in children

    MS MRI

    The first major scientific study into multiple sclerosis in children in the UK has begun at Birmingham Children’s Hospital to attempt to understand the debilitating condition.

    Researching doctors have been awarded a £400,000 grant by Action Medical Research and the MS Society, one of the largest it has ever given out.

    The study will follow a group of children for five years to give more insight into how MS progresses from an early age, and increase understanding of the condition among doctors caring for children and young people.

    Dr Doug Brown, biomedical research manager for the MS Society, said: “If we can pin down what happens very early on in MS, this will give us vital clues as to how the condition develops in adulthood.

    “MS isn’t considered to be a childhood condition but we need to beat this misconception because it makes life tougher for those young people who live with it day in, day out.”

    Current research into the number of children affected by MS is poor, but suggests that the onset of the condition occurs before the age of 16 in 0.4 to 10.5 per cent of cases, which could be anything up to 9,000 people in the UK.

    Dr Evangeline Wassmer is leading the study in Birmingham with other centres in Oxford, Bristol, Nottingham and London taking part.

    Source: Birmingham  © 2009 Trinity Mirror Midlands Limited

    Report reveals the importance of studying Multiple Sclerosis in children

    MS MRI

    An article published in the Spring 2009 edition of Multiple Sclerosis Quarterly Report, a joint publication of United Spinal Association and the North American Research Committee on Multiple Sclerosis (NARCOMS), reveals the importance of understanding the biological onset of Multiple Sclerosis in children as it can also lead to a greater understanding and treatment of MS in adults.

    The article by Jean Marie B. Ahorro, MD and Brenda L. Banwell, MD of The Hospital for Sick Children in Toronto, Ontario Canada, highlights some of the latest information on paediatric MS, including risk factors, diagnosis, symptoms, and treatment strategies.

    Presently, most care models for paediatric MS are based on protocols optimized in adults and pivotal studies of MS therapies are restricted to patients over 18 years of age. Conducting randomized control trials of paediatric MS has also been challenged by the rarity of the disease in children.

    Brenda L Banwell, MD states, "By virtue of their young age, children are inherently closer to the biological onset of the MS disease process, and have a time-limited opportunity to have experienced irrelevant exposures. As such, research into MS triggers and understanding of the earliest aspects of immune dysregulation are particularly important in the paediatric MS population."

    Banwell adds, "With respect to the International Paediatric MS initiative, I believe that the collective expertise will provide a strong rationale for prioritisation of trials of MS-medication in paediatric MS, and will be essential to achieve the patient numbers required for such trials."

    The authors discuss the benefits of creating paediatric-specific MRI diagnostic criteria that are more sensitive and specific to children since the appearance of paediatric MS is not entirely similar to that of adult-onset.

    Source: Market Watch © 2009 MarketWatch, Inc. (06/03/09)

    Relapses more frequent in patients diagnosed with paediatric-onset multiple sclerosis

    MS Brain

    Patients who develop multiple sclerosis before age 18 appear to experience more relapses of symptoms than those diagnosed with the disease as adults, according to a report in the January issue of Archives of Neurology.

    "Although the clinical onset of multiple sclerosis (MS) typically occurs between ages 20 and 40 years, 2.7 percent to 10.5 percent of patients have been reported to develop their first symptoms before their 18th birthday," the authors write as background information in the article. Previous reports suggest the progression of MS—an inflammatory disease in which myelin, the protective coating covering nerve cells, degenerates—is slower in patients who are diagnosed in childhood.

    Mark P. Gorman, M.D., of Brigham and Women's Hospital and Massachusetts General Hospital, Boston, and colleagues studied 110 patients diagnosed with relapsing-remitting MS in adulthood (average age at diagnosis, 34.4) and 21 with paediatric-onset MS (average age at diagnosis, 15.4). Relapsing-remitting is the most common type of MS, in which patients experience periods of symptoms followed by periods of symptom-free remission. Study participants developed their first symptoms in July 2001 or later, were monitored with semi-annual neurological examinations and were followed for 12 months or longer (an average of 3.67 years for paediatric-onset patients and 3.98 years for adult-onset).

    Patients who developed the disease in childhood had, on average, a higher yearly rate of relapses than those who were diagnosed as adults (1.13 vs. 0.4 relapses per year). "These findings persisted in multivariate regression models when controlling for sex, race and proportion of disease spent undergoing disease-modifying treatment and when age at onset was treated as a continuous variable," the authors write.

    "In general, the disease course of MS has been divided into a relapsing-remitting phase, during which inflammatory mechanisms predominate, and a secondary progressive phase, during which neurodegenerative mechanisms predominate," they continue. "Acute relapses are the clinical hallmark of the inflammatory phase of MS. The higher relapse rate in the paediatric-onset group in our study may therefore suggest that patients with paediatric-onset MS are coming to medical attention closer to the true biological onset of their disorder than patients with adult onset during a more inflammatory phase, as has been previously suggested."

    If patients with paediatric-onset diseases do indeed have more relapses despite their disease progressing more slowly, "this discrepancy may suggest greater plasticity, less neurodegeneration and potentially more repair and remyelination in the younger nervous system. Further study of the biological basis for this discrepancy may yield insight into the apparent disconnect between relapses and long-term disability progression."

    Source: JAMA and Archives Journals Arch Neurol. 2009;66[1]:54-59 (13/01/09)

    Tysabri (Natalizumab) use in paediatric Multiple Sclerosis


    Background  Natalizumab, a humanized monoclonal antibody raised against 4 integrins, is approved for treatment of active relapsing-remitting multiple sclerosis (RRMS) in adult patients.

    Objective  To determine the safety, effectiveness, and tolerability of natalizumab use in pediatric patients with MS.

    Design  Case report.

    Setting  Center for MS in childhood and adolescents, Göttingen, Germany.

    Patients  Three pediatric patients with RRMS having a poor response to other immunomodulatory therapies or having intolerable adverse effects.

    Interventions  Natalizumab given every 4 weeks at a dosage of 3 to 5 mg/kg of body weight.

    Main Outcome Measures  Cranial magnetic resonance (MR) imaging before treatment and every 6 months thereafter.

    Results  During 24, 16, and 15 months of treatment, no further relapses occurred in the 3 pediatric patients; all reported significant improvement in their quality of life. Follow-up MR imaging showed no new T2-weighted lesions or gadolinium-enhancing lesions. No adverse events were seen when dosage was adjusted to body weight.

    Conclusions  Natalizumab treatment was effective and well tolerated in our paediatric patients with RRMS who did not respond to initial immunomodulatory treatments. Therefore, it is a promising second-line therapy for paediatric patients with RRMS.

    Peter Huppke, MD; Wiebke Stark, MD; Claudia Zürcher, MD; Brenda Huppke, MD; Wolfgang Brück, MD; Jutta Gärtner, MD

    Author Affiliations: Departments of Pediatrics and Pediatric Neurology (Drs P. Huppke, Stark, Zürcher, B. Huppke, and Gärtner) and Neuropathology (Dr Brück), Faculty of Medicine, Georg August University, Göttingen, Germany.

    Source: Arch Neurol. 2008;65(12):1655-1658. (09/12/08)

    Hepatitis B immunisation does not generally increase the risk of multiple sclerosis
    Most of the children immunised against hepatitis B are not at an increased risk of developing multiple sclerosis (MS), but those who received a certain type of the vaccine are, according to a new study.

    The France based study involved 349 children with MS and 2,941 healthy children, all under 16. A total of 24.4 percent of them with MS were vaccinated for hepatitis B in the three years before the study, compared to 27.3 percent for the children without MS.

    Although the study found that hepatitis B vaccination does not generally increase the risk of multiple sclerosis, the children with MS were 1.74 times more likely to have received a certain type of hepatitis B vaccine, called Engerix B.

    Those children with MS developed symptoms three or more years after the vaccine. The risk was only found for this specific type of hepatitis B vaccine and not found for all vaccines against hepatitis B.

    This association cannot be taken as confirmation that the vaccine caused MS. Further studies are needed to determine whether this is a causal relationship, according to a statement by the American Academy of Neurology. The findings will be published in the October online issue of Neurology, the journal of the academy.

    Source: Thaindian news (26/09/08)

    Scientists link low vitamin D to Multiple Sclerosis risk in children

    Vitamin D

    Canadian researchers say they have found new links between low levels of vitamin D in children and an increased risk that they may develop multiple sclerosis.

    Speaking at an international meeting of MS specialists in Montreal, Dr. Brenda Banwell said that low levels of vitamin D in some children may explain why doctors are seeing more kids developing MS in Canada and other parts of the world.

    "What we found is the children with the lowest vitamin D levels were far more likely to be diagnosed with multiple sclerosis than were children who had healthier levels of Vitamin D," she said.

    Banwell and a team of scientists measured vitamin D levels from more than 100 children suffering what could be a first attack of MS.

    Of those with the highest blood levels of the so-called "sunshine vitamin," only six percent went on to develop full-blown MS within the next two years. Twenty-seven percent developed MS among those with the lowest levels of the vitamin.

    Multiple sclerosis is a chronic disease that attacks the central nervous system. Past studies have linked the disease, which affects about 55,000 Canadians, to environmental and genetic factors.

    Researchers say low vitamin D levels are epidemic among children, and people without enough vitamin D are at risk for bone problems.

    Doctors also believe that vitamin D may help keep the immune system functioning normally.

    Researchers say too many Canadian children are not getting enough of the vitamin, which may be obtained naturally from sunshine.

    "Children are indoors more they are on computers more, they play outdoors far less, but the consequence is, of course, they are getting little sunlight and little vitamin D," Banwell said.

    Researchers are now trying to see if boosting vitamin D levels in kids with MS could help treat the disease and put it into remission. They're also trying to see if vitamin D can prevent the onset of the disease.

    Source: © 2008 BERNAMA (21/09/08)

    Prognostic factors for paediatric Multiple Sclerosis after a first attack of inflammatory CNS demyelination

    MRI of MS Brain

    OBJECTIVE: To identify clinical, radiologic, or CSF factors that predict conversion to multiple sclerosis (MS) after a first attack of inflammatory demyelination in children.

    METHODS: In this nationwide retrospective multicenter study in the Netherlands, 117 children below age 16 were included. Fifty-four children presented with a monofocal clinically isolated syndrome (CIS) and 63 children with a polyfocal CIS (PCIS).

    RESULTS: A second MS-defining attack occurred in 43% of the CIS cases, compared to 21% of the patients with PCIS onset (p < 0.006). Basal ganglia and thalamic lesions and lesions larger than 2 cm on MRI (considered typical of ADEM) were observed during PCIS, irrespective of the presence of encephalopathy. No significant difference in developing MS was found in children with PCIS with or without encephalopathy. Elevated IgG index and presence of oligoclonal CSF bands were more often observed in children who developed MS. Both Barkhof and KIDMUS MRI criteria shared a high specificity and had a high positive predictive value for conversion to MS. In children under the age of 10, the Barkhof criteria had a higher sensitivity than the KIDMUS criteria, but still lower than in older children.

    CONCLUSIONS: Barkhof and KIDMUS MRI criteria share a high specificity and positive prognostic value for conversion to multiple sclerosis (MS). Sensitivity of these criteria is poor, especially in children below 10 years of age. Basal ganglia lesions can occur in patients who later develop MS. A substantial number of patients presenting with polyfocal onset and no encephalopathy remained monophasic.

    Source: PubMed PMID: 18672475 (13/08/08)

    Paediatric Multiple Sclerosis Linked to Cognitive Impairment

    Multiple sclerosis in childhood and adolescence, a relatively rare form of the disease, is associated with impaired cognitive function and low IQ, say investigators.

    More than half of a group of children and adolescents with MS had some degree of cognitive impairment, and almost a third had severe impairment, Maria Pia Amato, M.D., of the University of Florence, and colleagues in the MS Study Group of the Italian Neurological Society reported in the May 13 issue of Neurology.

    Additionally, almost 10% of the young patients had a low IQ (<70), which appeared related to earlier age at onset of MS.

    "We observed prominent defects of verbal and visuospatial memory, complex attention, and aspects of executive functions," the authors said. "Extrapolation of these findings would predict a high functional impact, because skills involving these faculties are increasingly emphasized in the higher academic degrees."

    About 5% of MS cases occur in children and adolescents -- roughly 500 a year in the U.S. The disease's impact on cognitive function is hypothesized to be more dramatic in children than with adults with MS, the authors said.

    Dr. Amato and colleagues reported findings from the largest study of the cognitive effects of MS in young patients, including 63 MS patients (mean age 15.8) and 57 age-matched healthy controls.

    Both groups completed a battery of neuropsychologic tests that assessed IQ, memory, attention/concentration, executive functions, and language. The investigators also assessed fatigue and depression in the patients and the control group.

    MS duration averaged three years, all patients had relapsing-remitting MS, and the mean disability score was 1.5. Forty patients had been treated with disease-modifying drugs, primarily interferon-beta. Duration of treatment averaged 1.3 years.

    The patients' mean IQ was 101.3 versus 120.5 for the control group. Because the control group's score was in the superior range, investigators compared also compared the patients' scores with a subgroup of 40 controls, whose IQ averaged 106.2.

    Two thirds of the patients versus 95% to 96% of the control group had IQ scores of 90 or higher. Seventeen patients (28%) had an IQ of 70 to 89, and five (8.6%) had an IQ <70 compared with two members (3.5%) of the controls. The only significant predictor of IQ <70 in the MS patients was earlier disease onset (P=0.009).

    Nineteen patients (31%) met criteria for severe cognitive impairment (failure on three tests), and 32 (53%) failed at least two tests, the principal criterion for milder forms of cognitive impairment. The 19 patients with severe impairment had a mean IQ of 81.2, compared with 109.8 for the rest of the patients. Low IQ was the only correlate of cognitive impairment.

    Three fourths of the patients met criteria for significant fatigue, pointing to a need to assess and treat fatigue in pediatric MS patients, the authors said. The patients had a depression prevalence of 6%.

    Source: Medpage Today © 2004-2008 MedPage Today, LLC (13/05/08)

    Evidence of thalamic grey matter loss in paediatric multiple sclerosis.

    OBJECTIVE: We used voxel-based morphometry (VBM) to assess the pattern of regional grey matter (GM) loss in patients with paediatric multiple sclerosis (MS) and its relation with the Expanded Disability Status Scale (EDSS) score, disease duration, and the extent of T2 lesion load (LL).

    METHODS: From 28 patients with paediatric relapsing-remitting MS (16 girls; mean age = 14.4 years, range = 7 to 16 years) and 21 matched controls, dual-echo and three-dimensional T1-weighted magnetization prepared rapid acquisition gradient echo sequences were acquired. T2 LL was measured using a local thresholding segmentation technique. Data were analyzed using an optimized VBM analysis and statistical parametric mapping.

    RESULTS: In paediatric patients with MS, mean brain T2 LL was 7.8 mL +/- 11.3. Intracranial volume did not differ between patients and controls. Compared to controls, patients with paediatric MS had significant GM loss in the thalamus, bilaterally, which was significantly correlated with T2 LL (r = -0.80 for the right thalamus, r = -0.74 for the left thalamus, p < 0.05, corrected for multiple comparisons). No correlation was found between thalamic GM loss, disease duration, and disability.

    CONCLUSIONS: In patients with paediatric multiple sclerosis (MS), differently from what happens in adult-onset MS, grey matter (GM) atrophy seems to involve the thalamus only, with sparing of the cortex and other deep GM nuclei. The correlation found between atrophy and T2 lesion load suggests transsynaptic and Wallerian degenerations as the most likely substrate of tissue loss in the thalamus of these patients.

    Mesaros S, Rocca MA, Absinta M, Ghezzi A, Milani N, Moiola L, Veggiotti P, Comi G, Filippi M.

    Neuroimaging Research Unit, Scientific Institute and University Hospital San Raffaele, Via Olgettina 60, 20132 Milan, Italy.

    Source: Pubmed 18272867 (04/04/08)

    Seoul National University, Medical Department reports on research in paediatric multiple sclerosis
    According to recent research from Seoul, South Korea, "To study the clinical characteristics of multiple sclerosis and associated optic neuritis in Korean children. A retrospective analysis was performed on 10 patients with an onset of multiple sclerosis before age 16."

    "Information on sex, age of onset, clinical course, laboratory findings, and clinical characteristics of optic neuritis was obtained. The mean age at presentation was 7.31 +/- 2.99 years, and the mean duration of observation was 36.2 +/- 26.1 months. No female predilection (50%) was observed. The disease presented as relapsing-remitting type multiple sclerosis in all patients and transited to secondary progressive type in two cases (20%). No oligoclonal bands were found in any patient.

    Optic neuritis occurred in eight patients (80%); five (62.5%) of these had optic neuritis at the first multiple sclerosis attack, with all five manifesting bilateral simultaneous optic neuritis. Visual acuity recovered to >= 20/40 in 8 of 15 eyes (53.3%), but in 2 eyes (13.3%) visual acuity remained at <= 20/200. In the patients with optic neuritis, the patients who showed optic neuritis at initial presentation had a worse visual prognosis (p = 0.030, Mann-Whitney, U-test). In Korean children with multiple sclerosis, age of onset was younger than reported in other countries, and there was no female predominance," wrote J.S. Hwang and colleagues, Seoul National University, Medical Department.

    The researchers concluded: "The prognosis for good visual acuity was worse inpatients who initially presented with optic neuritis.'."

    Hwang and colleagues published their study in the Journal of Aapos (Clinical characteristics of multiple sclerosis and associated optic neuritis in Korean children. Journal of Aapos, 2007;11(6):559-563).

    Source: NewsRX © 2008 NewsRx (05/03/08)

    Paediatric Multiple Sclerosis cases on the rise across U.S.

    Nationwide in the US, there are about 400,000 cases of multiple sclerosis. An increasing trend, however, is the diagnosis of this disease in children under the age of 18. It is now believed that one to five percent of all MS cases begin in children. Dr. Jayne Ness, associate professor of Pediatric Neurology at UAB, is determined to put a stop to this trend.

    “My interest in this area of study is patient driven,” said Ness. “When I was a fellow in training, I was always trying to figure out what type of disease was affecting these kids. Throughout my training and beyond, I kept in touch with a lot of them and eventually put a project together. In the 1990’s, several therapies became available for adults who had multiple sclerosis; however, these were not applicable in children. We wanted to determine whether these treatments could be used safely in children with MS, but we also had to be careful to make sure the diagnosis of MS was correct since some children have diseases that mimic MS.”

    MS is a disease in which a person’s immune system attacks the insulation surrounding nerve fibers in the brain and spinal cord. This material is composed of fats and proteins and, when damaged, prevents efficient conduction of electrical currents in the nervous system. This is a process much akin to a damaged wire on an electrical appliance such as a television, which causes a short circuit and, consequently, no “Desperate Housewives” tonight. As a result of the disease, people who have MS experience difficulty with movement, speech, balance and eyesight.

    “He began to see with double vision and had very bad headaches,” said Brandon Enea of his now 15 year old son, Collin. “We took him to a local doctor, who gave us a real scare the first night. We were told that he did not have a tumor, but, other than that, no one could tell us what was wrong with him. The doctor suggested that we take him to the Children’s Hospital immediately, so we put Collin in the car and drove as fast as we could.”

    On a regular basis, Ness sees patients from all over the southeast who have stories just like that of Collin. With funding from the National Multiple Sclerosis Society, Ness started the Center for Pediatric Onset Demyelinating Disease, where she and an entire team of doctors, nurses and researchers care for patients who are under the age of 21. CPODD is located in Children’s Hospital of Alabama and is one of only six Pediatric Multiple Sclerosis Centers of Excellence in the country.

    “Because of the grant funding from the National Multiple Sclerosis Society, we have been able to do more organized studies of these kids,” said Ness. “By forming the CPODD team, we were trying to cover as many bases as possible; hopefully, this has also improved patient care.”

    Indeed, patients and their families are satisfied with the level of care that they receive at the CPODD.

    “The team here is amazing, everybody has been absolutely amazing,” said Rita Henry of her 17 year old daughter Leslie. “Leslie was 16 years old when she was diagnosed. Her first episode lasted two months and included numbness on the left side of her body, weakness, lost vision and slurred speech. No one could understand what she was saying. We have had to change everything about our daily life in order to get through that period. As a single parent, it has not been an easy process, but the CPODD team has helped tremendously.”

    Leslie now leads a fairly typical teenage life, participating in numerous school and church activities such as the show choir, student council and the praise team; she is also a cheerleader at her high school. Moreover, in a matter of months, Leslie will be leaving home to attend Jackson State University, an accomplishment for people who have MS that was unheard-of in recent history.

    “We know first-hand that people with MS can lead a normal life,” said Henry. “I think Leslie can be a spokesperson to help other kids who have been diagnosed with MS and encourage them to continue pursuing their dreams.”

    Ness and her CPODD team plan to continue standing right beside patients and their families, supporting them every step of the way.

    “We want to do everything we can to help people cope with this lifelong illness,” said Ness. “I believe that the future of MS is pretty bright. New therapies will soon arise that can be taken orally and eliminate the need for patients to receive injections. Ultimately, we hope to one day see a cure.”

    Source: Kaleidoscope © 2008 The University of Alabama at Birmingham (27/02/08)

    How Multiple Sclerosis Affects Children
    What happens when children are diagnosed with multiple sclerosis?

    Debbie Andalo on the work being done to help them cope with a disease largely thought to affect only adults

    Karen Pumpuni could be any ordinary teenager enjoying her half-term break. In her skinny jeans and T-shirt she crouches over her computer, breakfast on her lap, finishing off her AS-level English coursework. Only the wheelchair folded away in the corner of her home in Streatham, south London, gives a clue that her life is far less ordinary than that of other 16-year-olds. For the last two years Karen and her family have been coming to terms with her diagnosis of the neurological disease multiple sclerosis, which has only recently been acknowledged by the medical profession as a condition that affects children.

    Karen is one of around five per cent of the 100,000 people in the UK with MS who are children. The chronic condition, traditionally associated with adults, affects the central nervous system creating symptoms of fatigue, loss of mobility and eyesight, and can result in long-term disability. It took doctors four years to diagnose Karen's condition, which came as a shock to her mother Eunice but also a relief.

    She says: "I felt relief that Karen had been given a diagnosis. I had hoped that she would be diagnosed with something that would be instantly curable. At the same time I thought that the doctors might have made a mistake because I had never hard of children getting MS before and when I went home and looked on the internet there was nothing I could find out about it."

    Karen was completely in the dark about the disease, which affects twice as many women as men. "I had heard about MS but I didn't know the symptoms like you would if it was cancer," she said. "I didn't know if it was something severe or something which could be easily treated like asthma." Two years on from her diagnosis she still feels isolated by the disease. She admits: "I feel like nobody understands what I go through."

    This week the charity the MS Society is hoping that its first ever conference on childhood MS, held on Wednesday (November 7) in London, will go someway to help raise the public and health profession's understanding of the life that Karen and other young people like her face. The charity hopes that the conference will be the first step in the UK towards recognition of the condition in children, taking the lead from US and Canada.

    The conference will aim to decide best practice for children with MS in the UK and look to where services need to be developed. At the moment the UK has only one dedicated centre for children with MS at the Birmingham children's hospital, and even there, no specialist MS nurses are trained to work with children.

    Dr Evangeline Wassmer, the paediatric neurologist who heads the unit, says: "A lot of children with MS get seen by adult neurological services or get some shared care with paediatrics. It's a big issue – they are children and they need to be communicated with as children, it's not just a question of talking to their parents."

    Dr Wassmer wants more dedicated MS children's centres and national prescribing guidelines changed so that the disease modifying drugs available for MS can routinely be given to children without prior approval of their primary care trust.

    She is also keen to establish a longitudinal study of MS in children so that the disease can be tracked from a young age to adulthood. "At the moment we don't have that data, we don't know what happens to the disease if its onset is in childhood."

    Dr Anita Rose is a specialist clinical psychologist for people with MS at the Walton centre of neurology and neurosurgery in Liverpool. While the centre is for adults with MS, she takes some child referrals and gives advice and support to health care professionals and families of young people with MS. She wants the UK to follow the US model and establish summer camps for children with MS as one way of breaking down their isolation. Social networking websites and YouTube could also be used, she suggests, to put young people in contact with each other.

    She says: "It's a very isolating diagnosis. Children are very often scared, they get angry and depressed. They may know it's not a terminal condition, in fact the first question they ask is 'Am I going to die?' But they realise they may become disabled, that it's a life-long condition and they could be in a wheelchair by the age of 25."

    This September the MS Society committed itself to dedicating "a year of youth", provisionally for 2009. This will highlight the issue of childhood MS, what it means for children and their families, as well as those young people who care for an adult parent with MS.

    Details of the initiative are likely to be raised at Wednesday's conference, says Jayne Spink, the charity's director of policy and research. She says: "At the moment the charity doesn't provide anything for children or young adults with MS in terms of articles or information, because it's only recently that we have become aware of the whole issue."

    She is hopeful that following the conference some of those gaps, and others, will be identified and filled. "We want to look at the best way of providing care and expertise. We want to find out what is being done for children, what we need to do and how we can bring that forward."

    Source: Guardian Unlimited (05/11/07)

    Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions

    The onset of multiple sclerosis (MS) in childhood poses diagnostic and therapeutic challenges, particularly if the symptoms of the first demyelinating event resemble acute disseminated encephalomyelitis (ADEM). MRI is an invaluable diagnostic tool but it lacks the specificity to distinguish ADEM from the first attack of MS.

    Advanced MRI techniques might have the required specificity to reveal whether the loss of integrity in non-lesional tissue occurs as a fundamental feature of MS. Although the onset of MS in childhood typically predicts a favourable short-term prognosis, some children are severely disabled, either physically or cognitively, and more than 50% are predicted to enter the secondary-progressive phase of the disease by the age of 30 years.

    Immunomodulatory therapies for MS and their safe application in children can improve long-term prognosis. Genetic and environmental factors, such as viral infection, might be uniquely amenable to study in paediatric patients with MS. Understanding the immunological consequences of these putative exposures will shed light on the early pathological changes in MS.

    Source: The Lancet Neurology (20/09/07)

    Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study.

    BACKGROUND: The full spectrum of clinical manifestations and outcome, and the potential importance of regional or demographic features or viral triggers in paediatric multiple sclerosis (MS), has yet to be fully characterised. Our aim was to determine some of these characteristics in children with MS.

    METHODS: 137 children with MS and 96 control participants matched by age and geographical region were recruited in a multinational study. They underwent structured clinical-demographic interviews, review of academic performance, physical examination, disability assessment (MS patients only), and standardised assays for IgG antibodies directed against Epstein-Barr virus, cytomegalovirus, parvovirus B19, varicella zoster virus, and herpes simplex virus.

    FINDINGS: MS was relapsing-remitting at diagnosis in 136 (99%) children. The first MS attack resembled acute disseminated encephalomyelitis (ADEM) in 22 (16%) of the children, most under 10 years old (mean age 7.4 [SD 4.2] years). Children with ADEM-like presentations were significantly younger than were children with polyfocal (11.2 [4.5] years; p<0.0001) or monofocal (12.0 [3.8] years; p=0.0005) presentations. Permanent physical disability (EDSS>/=4.0) developed within 5 years in 15 (13%) of the 120 children for whom EDSS score was available. 23 (17%) had impaired academic performance, which was associated with increasing disease duration (p=0.02). Over 108 (86%) of the children with MS, irrespective of geographical residence, were seropositive for remote EBV infection, compared with only 61 (64%) of matched controls (p=0.025, adjusted for multiple comparisons). Children with MS did not differ from controls in seroprevalence of the other childhood viruses studied, nor with respect to month of birth, sibling number, sibling rank, or exposure to young siblings.

    INTERPRETATION: Paediatric MS is a relapsing-remitting disease, with presenting features that vary by age at onset. MS in children might be associated with exposure to EBV, suggesting a possible role for EBV in MS pathobiology.

    Banwell B, Krupp L, Kennedy J, Tellier R, Tenembaum S, Ness J, Belman A, Boiko A, Bykova O, Waubant E, Mah JK, Stoian C, Kremenchutzky M, Bardini MR, Ruggieri M, Rensel M, Hahn J, Weinstock-Guttman B, Yeh EA, Farrell K, Freedman M, Iivanainen M, Sevon M, Bhan V, Dilenge ME, Stephens D, Bar-Or A.

    Division of Neurology, The Hospital for Sick Children, University of Toronto, ON, Canada; Research Institute, The Hospital for Sick Children, University of Toronto, ON, Canada.

    Source: Lancet Neurol. 2007 (11/08/07)

    Children: More Sun Less Multiple Sclerosis

    People who spent more time in the sun as children may have a lower risk of developing multiple sclerosis (MS) than people who had less sun exposure during childhood, according to a study published in the July 24, 2007, issue of Neurology®.

    For the study, researchers surveyed 79 pairs of identical twins with the same genetic risk for MS in which only one twin had MS. The twins were asked to specify whether they or their twin spent more time outdoors during hot days, cold days, and summer, and which one spent more time sun tanning, going to the beach and playing team sports as a child.

    The study found the twin with MS spent less time in the sun as a child than the twin who did not have MS. Depending on the activity, the twin who spent more hours outdoors had a 25 to 57 percent reduced risk of developing MS. For example, the risk of developing MS was 49 percent lower for twins who spent more time sun tanning than their siblings.

    “Sun exposure appears to have a protective effect against MS,” said study authors Talat Islam, MBBS, PhD, and Thomas Mack, MD, MPH, with the Keck School of Medicine of the University of Southern California in Los Angeles. “Exposure to ultra violet rays may induce protection against MS by alternative mechanisms, either directly by altering the cellular immune response or indirectly by producing immunoactive vitamin D.”

    The study also found the protective effect of sun exposure was seen only among female twin pairs, but Mack says this novel finding must be viewed with caution since only a few male twins were involved in the study.

    “Our findings note the importance of sun exposure among people with identical genetic risk for MS,” said Mack. “High priority should be given to research into how sun exposure reduces MS risk if we are to unravel the mystery of what causes MS.”

    Source: American Academy of Neurology (24/07/07)

    Natural History of Multiple Sclerosis with Childhood Onset

    The course and prognosis of childhood-onset multiple sclerosis have not been well described.

    We used data from 13 adult neurology departments affiliated with the European Database for Multiple Sclerosis (EDMUS) network to identify a cohort of 394 patients who had multiple sclerosis with an onset at 16 years of age or younger and a comparison group of 1775 patients who had multiple sclerosis with an onset after 16 years of age. We determined the initial clinical features, the dates of disease onset, and the occurrence of outcomes, including relapse, conversion to secondary progression, and irreversible disability as measured by scores of 4 (limited walking ability but ability to walk more than 500 m without aid or rest), 6 (ability to walk with unilateral support no more than 100 m without rest), and 7 (ability to walk no more than 10 m without rest while using a wall or furniture for support) on the Kurtzke Disability Status Scale (range, 0 to 10; higher scores indicate more severe disability).

    For patients with childhood-onset multiple sclerosis, the estimated median time from onset to secondary progression was 28 years, and the median age at conversion to secondary progression was 41 years. The median times from onset to disability scores of 4, 6, and 7 were 20.0, 28.9, and 37.0 years, respectively, and the corresponding median ages were 34.6, 42.2, and 50.5 years. In comparison with patients with adult-onset disease, those with childhood-onset disease were more likely to be female than male (female:male ratio, 2.8 vs. 1.8), were more likely to have an exacerbating–remitting initial course (98% vs. 84%), took approximately 10 years longer to reach secondary progression and irreversible disability, and reached these landmarks at an age approximately 10 years younger (P<0.001 for all comparisons).

    Patients with childhood-onset multiple sclerosis take longer to reach states of irreversible disability but do so at a younger age than patients with adult-onset multiple sclerosis.

    Source Information
    From Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon; INSERM Unité 842; and Université Lyon 1 — all in Lyon (C.R., S.V., C.C.); Hôpital de Bicêtre, Paris Kremlin-Bicêtre, Paris (Y.M., M.T.); Hôpital Pontchaillou, Rennes (G.E.); Hôpital Purpan, Toulouse (M.C.); Hôpital Saint Julien, Nancy (M.D.); Hôpital Pellegrin, Bordeaux (B.B.); Hôpital Pasteur, Nice (C.L.-F.); Hôpital de la Timone, Marseille (J.P.); Hôpital Général, Dijon (T.M.); Hôpital de la Pitié–Salpêtrière, Paris (C.L.); Hôpital Roger Salengro, Centre Hospitalier Régional Universitaire, Lille (P.V.); Hôpital Tenon, Paris (E.R.); and Centre Hospitalier Universitaire Dupuytren, Limoges (L.M.) — all in France; University Hospital Gasthuisberg, Leuven, Belgium (B.D.); and Royal Victoria Hospital, McGill University, Montreal (C.R., S.S.).

    Source: The New England Journal of Medicine © 2007 Massachusetts Medical Society. (21/06/07)

    Childhood-Onset MS in Isfahan is high
    Iranian researchers have said the rate of childhood multiple sclerosis in Isfahan is high because of geographical or ethnic differences.

    Although multiple sclerosis is considered as an inflammatory demyelinating disease of young adults, nearly 3% of patients manifest it under the age of 16 years. The aim of this study was to highlight the clinical and demographic features of early-onset multiple sclerosis in Isfahan, Iran.

    This prospective study concerned multiple sclerosis patients in whom the disease started before the age of 16 years and who were referred to the only clinic of multiple sclerosis in Isfahan. All early-onset multiple sclerosis patients underwent magnetic resonance imaging. Magnetic resonance imaging findings were analysed according to the Barkhof's criteria. All early-onset multiple sclerosis patients were followed for a mean period of 4.7 years.

    Among 1,238 multiple sclerosis patients, 82 early-onset multiple sclerosis patients were identified. The female to male ratio was 4.5:1. The mean age of onset was 14.1 (range: 5 to 16) years. In 53 (65%) patients, the onset was monosymptomatic; in the remaining 29 (35%), it was polysymptomatic.

    Source: Press TV © Press TV 2007. All rights reserved. (30/04/07)

    UCSF Team Battles Paediatric MS
    Multiple sclerosis is typically thought of as a neurological disorder affecting adults. But children get it too. With advancements in technology, more young people are being diagnosed earlier. UCSF is one of six centers of excellence focused on paediatric MS and funded by the National MS Society. It's the only centre for kids west of the Rockies.

    Dr. Dorothee Chabas is a neurologist specialising in multiple sclerosis. The debilitating neurological condition identified by lesions on the brain. Every Tuesday, she's part of a multidisciplinary team at UCSF meeting with young patients and their families. A social worker, paediatric neurologist, neurologist and pediatric neuropyschologist, all listen together and offer input.

    Twelve-year-old Samantha Richards found out last May her double vision and balance problems were actually symptoms of MS -- an MRI detected the lesions in her brain.

    Samantha Richards, multiple sclerosis patient: "I am getting used to taking the medicines, it's just that it hurts, no matter what."

    Multiple sclerosis affects about 400,000 people in this country(US). About 10,000 of them are children or teens. And about 10 to 15 percent of adults diagnosed with MS say they remember having initial symptoms before the age of 18.

    Emmanuelle Waubant, MD, Ph.D.: "So what happens is either symptoms are mild enough that they are dismissed by the child or by the parents or by the physicians, or sometimes they're attributed to other diseases that are known to be more frequent in children."

    Neurologist Emmanuelle Waubant is Director of UCSF's paediatric MS clinic -- the only one west of the Rockies.

    Emmanuelle Waubant, MD, Ph.D.: "About 10 years ago, it was almost impossible to get a child with MS an authorisation to receive treatments that were authorised for adults."

    But today, most insurance covers the treatment. And most doctors feel comfortable prescribing drugs like Interferon, which help slow the progression of the disease. The six paediatric MS centres across the country operate as a network -- sharing information, discussing difficult cases and collecting data.

    Emmanuelle Waubant, MD, Ph.D.: "By building strong clinics, then we can develop very strong research as well."

    Research that could help provide important clues to what causes MS.

    Emmanuelle Waubant, MD, Ph.D.: "There is probably a set of environmental factors that contribute to the susceptibility of the disease and possibly to the course of the disease."

    Dorothee Chabas, MD, Ph.D., Neurologist: "We are trying to collect information from the very beginning and follow them up over time and I think that's a really unique opportunity to do research on MS in general."

    But one of the short term goals is simply getting the word out that multiple sclerosis exists in children -- letting community hospitals, paediatricians and internists know the signs.

    Emmanuelle Waubant, MD, Ph.D.: "It can be decreased vision, it can be decreased balance, double vision, weakness in one limb or tingling or numbness in different parts of the body."

    Mike Richards is just grateful his daughter's diagnosis came quickly and that the team of specialists is here for them at UCSF.

    Mike Richards, Samantha's father: "They speak to you as a human being that's got feelings, and they're really concerned and want the best for Sam."

    And together they decide on treatment options.

    The Richards are taking things one day at a time, while praying for answers.

    Mike Richards, Samantha's father: "Find out why it happens and find a cure for it so another child doesn't have to through it -- that would be the ultimate."

    This team at UCSF hopes together, they can help do just that.

    Source: ABC News Copyright ©2007 ABC Inc., KGO-TV San Francisco. (16/03/07)

    UAB Establishes Center For Pediatric-Onset Demyelinating Disease
    UAB (University of Alabama at Birmingham) has established a Center for Paediatric-Onset Demyelinating Disease (C-PODD), following action today by the UA System Board of Trustees.

    Demyelinating diseases are disorders of the central nervous system, affecting the myelin sheaths that support nerve fibers. Multiple sclerosis is the most common form of such diseases.

    Earlier this year, the National Multiple Sclerosis Society (NMSS) designated UAB’s pediatric-onset demyelinating disease clinic as one of six Paediatric Multiple Sclerosis Centers of Excellence in the country.

    “The establishment of this center, coupled with the earlier NMSS recognition, places UAB at the forefront of efforts to better understand these diseases and the effects of early onset on disease progression,” said Jayne M. Ness, M.D., Ph.D., assistant professor of paediatric neurology and center director.

    The center will provide state-of-the-art multi-disciplinary care and support for children, teens and families living with MS and other central nervous system demyelinating diseases.

    C-PODD also will build a multi-ethnic research cohort of children and teens from around the country with demyelinating disease. In conjunction with the NMSS and other pediatric MS centers, center researchers will study this patient population with respect to clinical presentation, neuroimaging, laboratory findings, treatment regimens, neurocognitive functioning, quality-of-life measures and long-term functional outcome.

    The center also will serve as a resource to provide up-to-date, accurate information about MS and related disorders to patients and families, schools, health care providers, funding agencies, third party payers, the scientific community and the public.

    While MS is considered an adult disease, there are 8,000 to 10,000 children who have the ailment, and another 10,000 to 15,000 who have experienced what may be symptoms of MS, according to the NMSS. The disease is more difficult to diagnose in children, and many paediatricians are not familiar with MS. Even when diagnosed, consensus guidelines for treatment exist only in relationship to adult MS, with none for children, largely because there is little information about MS in children.

    Source: UAB Media Center © 2005 University of Alabama at Birmingham (18/09/06)

    UCSF Opens Paediatric MS Center
    Early this year, the UCSF Medical Center opened a Regional Paediatric Multiple Sclerosis Center to address the needs of patients and their families. The paediatric MS center at UCSF is one of only six such clinics in the United States, all of which have opened under the sponsorship of the National Multiple Sclerosis Society.

    At the paediatric MS center, patients and their families are able to see, in one sitting, clinicians who are paediatric specialists and MS specialists. “Children have historically been referred to an adult MS specialist, who may not know about the finer points of how the disease acts and how it is best treated in children,” says Emmanuelle Waubant, MD, PhD. “The families are left with a lot of questions and challenges.”

    Patients coming to the paediatric MS center are evaluated and treated by a team that includes a paediatric neurologist and a nurse practitioner, adult MS specialists, a social worker and a neuropsychologist. “Parents say it’s a relief to be able to talk to all the specialists at once,” Waubant says. “Usually they shuttle from one to the next and often get conflicting or disconnected stories.”

    Because of the subtle and varied nature of the disease, different members of the team may have different opinions about diagnosis or treatment even though they are seeing the same patient at the same time, Waubant says. The discussions that such perspectives produce can be good for patients, she says. “By having specialists interact directly with one another, they can benefit from each other’s views and provide the best possible care for the patients.”


    USCF Regional Paediatric Multiple Sclerosis Center 

    UCSF Regional Paediatric Multiple Sclerosis Center Fact Sheet (pdf) 

    UCSF Awarded Grant for Paediatric Multiple Sclerosis Center - January 18, 2006

    Source: The University of California, San Francisco Copyright 2006 (18/07/06) 

    Multiple Sclerosis in Children Is More Common Than Thought
    Multiple sclerosis is increasingly being diagnosed in children and teens. Although physicians have long known that kids can come down with the disease, new technology and emerging awareness of the problem have led them to spot the kind of cases that previously had gone undetected until years later.

    Among the 400,000 cases of MS diagnosed in the United States, 10,000 are paediatric cases, although neurologists think that there are probably many other cases being missed. “There may be up to 20,000 children with MS,” says UCSF researcher Emmanuelle Waubant, MD, PhD.

    Even after diagnosis, children with MS and their parents are confronted by issues not faced by adult patients, Waubant says. After an MS diagnosis, children may be seen by adult neurologists who specialise in MS, but have little experience with children, or by paediatric neurologists who have little experience with the disorder, she says. The epidemiology and course of the disease are also different in children than in adults, and there may be a lack of information about the paediatric safety and efficacy of drugs used to treat adult MS. Such concerns have led to the creation of the newly opened UCSF Regional Paediatric MS Center

    How Multiple Sclerosis Manifests in Children

    Multiple sclerosis in children manifests itself differently than MS in adults, researchers say. In children, MS may begin after a first bout of neurological symptoms (called acute disseminated encephalomyelitis, or ADEM), which is felt to be temporary. “Most children with ADEM make a nice recovery and never have other symptoms, but a certain proportion continue to have symptoms and new symptoms occur later, thereby meeting the criteria of MS,” Waubant says.

    The disease is thought to progress more slowly in children, but that is debatable when looking at an ethnically mixed population, Waubant says. The epidemiology of the disease also presents a different picture in adults and children. In adults, women get MS more often than men, but until puberty, MS afflicts boys and girls equally. And while the adult disease predominates among whites, in paediatric patients the pattern is the reverse, says Waubant, with far higher incidence and possible severity among minority children.

    The cognitive consequences of MS are likely to be greater in children than in adults, possibly because children are still developing those skills and do not have sufficient cognitive capacity to fall back upon. “If children with MS are away from school for long periods, that only adds to the impact MS might have on their cognitive development,” Waubant says.

    Paediatric MS Might Teach Us Much About MS in General

    The study of paediatric MS offers the possibility of learning much more about the mysterious etiology of MS in general, researchers say. Multiple sclerosis has long been thought to have both genetic and environmental causes, but no specific environmental factor has been identified. In part, this is because the disease may strike long after exposure to such a factor. “Studying MS in children is offering a new window into studying environmental factors because the onset has to be much closer to the environmental exposure,” Waubant says.

    Physicians treating children with MS face other complications. Because drugs for MS are tested in adults, physicians have often been hesitant to administer them without knowing that they are safe and efficacious in children. “This was also important because families’ health insurance plans would deny coverage for these drugs,” Waubant says.

    Waubant led the first study of the safety of using interferon to treat MS in children. Since then, others have collected retrospective or prospective data to show that adult MS drugs are safe in children. Because of the nature of these studies, it will remain unclear how efficacious the drugs are in children.

    Source: The University of California, San Francisco Copyright 2006 (18/07/06)

    Multiple Sclerosis Risk Influenced by Childhood Environment
    Study of children and adults sheds new light on mysterious disease.

    The Multiple Sclerosis Society of Canada announced findings from a Canadian study that shows the risk of MS may be influenced by place of residence during childhood rather than ancestry. The study results were published in a recent edition of Neuroepidemiology.

    The study puts into question the belief that MS is a disease targeted primarily at Caucasians or those with ancestral ties to areas north of the equator such as Northern Europe.

    The study involved 44 children and 573 adults from the paediatric MS clinic at the Hospital for Sick Children and the adult MS clinic at St. Michael's Hospital, both located in Toronto.

    "By comparing study results with census data, we found that the MS population has become more multicultural as immigration to Ontario has increased," explains Dr. Brenda Banwell, director of the paediatric MS clinic at the Hospital for Sick Children and principal investigator for the study. "This adds great credence to our theory that childhood residence, more than ancestry, is a major determinant of MS risk."

    The adult MS clinic population examined showed most of the patients, upwards of 90 percent, reported European heritage. Data from the 1971 census, obtained when most of the adult MS patients were growing up in Ontario, showed 84 percent of residents of Ontario were of European ancestry.

    Meanwhile, paediatric MS patients were more likely to report Caribbean, Middle Eastern or Asian ancestry, accurately mirroring the population shift as detailed by the 2001 census.

    "The common thread in all of this is that 100 percent of the paediatric population and 79 percent of the adult population grew up in Ontario," says Dr. Banwell. "This, combined with the ancestry data, suggests a prevailing influence of environment on MS risk."

    According to the MS Society, this is an important study because the relative contributions of ancestry, country of birth and residence as determinants of MS risk have never been explored in the paediatric MS population.

    "The change in immigration patterns, and the presence of well-established paediatric and adult MS programs, provided researchers with the unique opportunity to evaluate these factors as determinants of MS risk," says Dr. William J. McIlroy, national medical advisor for the MS Society of Canada. "The more complete a picture we can paint of MS and its risk factors, the closer we will be to finding the cause, and ultimately, the cure."

    The study was funded by the MS Scientific Research Foundation which receives the majority of its funding from the MS Society of Canada.

    Source: Multiple Sclerosis Society of Canada (24/05/06)

    Paediatric MS cases on the rise in Canada
    Expert says some pediatricians don't view childhood MS as possible, and early cases risk being dismissed as a virus.

    When the Paediatric Multiple Sclerosis Clinic opened at Toronto's Hospital for Sick Children in 1999, physicians expected five to 10 patients a year. Last year, they had 48.

    Clinic director Dr. Brenda Banwell said each year at least 100 Canadian children are reported as having an initial attack (clinically isolated syndrome) and about 40 are diagnosed with the disease. But Dr. Banwell said she believes both these figures are under-representations.

    While reports of children with MS symptoms date back to the 1920s, widespread recognition has only come in the last decade.

    "I don't know if it's because MS is becoming that much more common or if it's because we are so much better at diagnosing it," she said. "I think it's a bit of 'if you build it, they will come' and now that paediatricians know what we do, we are seeing more kids. There is also more of the philosophy of getting an MRI right away."

    But better diagnostic tools and increased awareness aside, Dr. Banwell believes there are simply more children with MS.

    In April 2004, the Canadian Paediatric Society added MS to its Canadian Pediatric Surveillance Program, which sends every paediatrician in Canada monthly reminders of MS symptoms and asks them to report whether they saw cases.

    The program acknowledged one of the barriers to diagnosis is lack of awareness of MS as a possible outcome of acute demyelination in children.

    The possible outcomes of initial central nervous system demyelination include optic neuritis, transverse myelitis, hemisensory or hemi-motor syndromes, cerebellar or brainstem dysfunction or acute disseminated encephalomyelitis (ADEM).

    Predicting whether symptoms represent an acute attack or are the beginning of MS remains a challenge. Many paediatricians don't view MS as possible in children, as it is widely viewed as an adult-onset disease.

    When symptoms like weakness, tingling or impaired vision come and go, as they can in MS, Dr. Banwell says they're dismissed as viruses, stress or visual problems.

    "Saying it was just a virus will mean these kids will not be closely followed. And some of them may be at risk for further attacks," she said, pointing out a doctor may not link a future attack to the first episode, which would point to MS.

    But Dr. Banwell says because of the paediatric surveillance program and steps by the MS Society of Canada, paediatricians are quicker to look for MS.

    Supporting the family

    Dr. Brandon Meaney, head of neurology at McMaster Children's Hospital, agrees MS in children has been on paediatric neurologists' radar screens for some time, but some consciousness-raising has been needed in paediatricians.

    "There is more discussion and awareness because of the surveillance program. Paediatricians and trainees are requesting information from me on ADEM and MS. Before we were pursuing it, now they're coming to us."

    Dr. Meaney says about six kids a year in Hamilton are diagnosed with a demyelinating attack and one may go on to have MS.

    Dr. Peter Nieman, a community paediatrician in Calgary, says that in 20 years in practice he has never diagnosed MS and doesn't think he's ever missed a case. But he is open to the possibility of MS in children.

    "Things change. We used to say there's no way you get a stroke in kids, now we know that's not true," he said. "You have to be open to the possibility if it doesn't fit a particular diagnosis."

    Because diseases like MS are more the domain of specialists, Dr. Nieman sees the paediatrician's role as supporting the family after diagnosis. "Families sometimes struggle with things like this. The paediatrician's focus can be helping the family with the psychosocial issues that follow it."

    Dr. Marie-Emmanuelle Dilenge, a neurologist at Montreal Children's Hospital, said her department sees about two cases of MS a year and between five to 10 demyelinating episodes.

    Montreal Children's is part of a five-year study at 22 Canadian hospitals following children who have had an initial attack. Researchers will determine if a particular combination of symptoms in a child with a first attack is more likely to lead to MS. They will look at the immune system of children with a first attack and at patterns of damage in the brain and spinal cord to determine if certain patterns predict who will go on to develop MS.

    Dr. Dilenge said neurologists are seeing more diagnoses than expected and in children as young as six years old. "MS in children is still not well recognised by paediatricians or ophthalmologists, but I think it's coming," she said. "Doctors should be sure to think of a demyelinating event as a possibility and act on it faster with MRI."

    Dr. Banwell agrees early diagnosis is key. "We should not dismiss episodic demyelination as being benign. It could be the beginning of MS," she said. "In a disease like MS, the earlier the treatment, the better. This includes counselling, physiotherapy and medical. So recognition is very important."

    Source: The Medical Post © Copyright 2006 The Medical Post. All rights reserved.(11/04/06)

    Some Children Develop Food Immune Reaction
    Children with neurological autoimmune diseases develop immune reactions to other targets in their bodies and in food, says a U.S. study.

    Dr. Brenda Banwell of the Hospital for Sick Children in Toronto studied 166 children: 63 with an autoimmune demyelinating syndrome -- either multiple sclerosis or an isolated event of central nervous system autoimmunity -- 43 with type I diabetes -- also an autoimmune disease -- 31 with a non-autoimmune neurological condition and 30 healthy controls.

    They examined blood samples for T-cell proliferation in response to exposure to a variety of antigens, including myelin protein from nerve cells, proteins in the pancreas and proteins in milk.

    About one-quarter of these children also showed a response to proinsulin, a T-cell target in type I diabetes. More than 60 percent also responded to a protein in milk. Ninety percent of the children with type 1 diabetes responded to pancreatic antigens as expected, but 79 percent responded to myelin and 90 percent responded to milk protein.

    The responses seen against milk proteins raise the possibility that substances in food may be associated with autoimmunity, Barnwell told the American Academy of Neurology 58th annual meeting in San Diego.

    Source: United Press International (08/04/06)

    Sick Kids Researchers Look At Viral Triggers For Multiple Sclerosis In Children

    This is an older research article which I have just found, and thought it was very relevant to this page. Squiffs

    TORONTO - Researchers at The Hospital for Sick Children (Sick Kids) have shown an association between paediatric multiple sclerosis (MS) and the Epstein-Barr virus (EBV), indicating that exposure to the virus at a certain time in childhood may be an important environmental trigger for the development of MS. This research is reported in the April 21, 2004 issue of JAMA (The Journal of the American Medical Association).

    "Earlier studies suggested a relationship between childhood exposure to Epstein-Barr virus and the risk of developing MS. This is virtually impossible to quantify in adult MS patients, as nearly 90 per cent of the healthy adult population in Western countries has been exposed to EBV. In the paediatric patients, we can study viral exposures more easily, as children have fewer viral exposures due to their young age," said Dr. Brenda Banwell, the study's principal investigator, a Sick Kids neurologist and associate scientist, and an assistant professor in the Department of Paediatrics at the University of Toronto.

    The research team found that 83 per cent of the paediatric MS patients showed evidence of a past EBV infection, compared with 42 per cent for the healthy control group. The paediatric MS patients also were less likely than the control subjects to have been exposed to herpes simplex virus. Epstein-Barr virus is very common and transmissible virus in the herpes family that causes infectious mononucleosis.

    "We think the Epstein-Barr virus plays an important role in the development of MS, as the genetic code of the virus contains sequences that are identical to genetic sequences in the myelin basic protein, which is expressed in the brain, and destroyed in MS. It is conceivable that the immune system mounts a response to that genetic sequence in EBV, then sees it in myelin and targets it as well," added Dr. Banwell.

    Multiple sclerosis (MS) is a disease of the brain, spinal cord, and optic nerves that can cause problems with muscle control and strength, vision, balance, sensation (such as numbness or tingling in your feet or hands), and mental functions such as thinking (cognition) and moods.

    The symptoms of MS are caused by inflammation of the central nervous system and the destruction of myelin, the protein coating that surrounds and protects nerve fibres (axons).

    MS is believed to involve a complex interplay between environmental triggers (such as infections), genetic predisposition, and an abnormal autoimmune response. At least five per cent of all MS patients experience the onset of their disease before the age of 18. It is estimated that 50,000 Canadians have MS. Multiple sclerosis is the most prevalent in countries that are furthest from the equator, such as Canada, northern Europe, and Australia.

    "We suspect that it is the sequence and timing of viral exposure and how this modifies an individual's immune response that is important," said Dr. Banwell. "Children with MS are the closest to the biological onset of the disease, which allows us to look at a whole host of causative factors that are very difficult to study in adults."

    Other members of the research team included Dr. Suad Alotaibi (now at the Al-Sabah Hospital in Kuwait), and Julia Kennedy, Dr. Raymond Tellier, and Derek Stephens, all from The Hospital for Sick Children.

    This research was supported by The Hospital for Sick Children Foundation.

    The Hospital for Sick Children, affiliated with the University of Toronto, is Canada's most research-intensive hospital and the largest centre dedicated to improving children's health in the country. Its mission is to provide the best in family-centred, compassionate care, to lead in scientific and clinical advancement, and to prepare the next generation of leaders in child health.

    Source: Copyright © 1995-2006 ScienceDaily LLC

    Jacobs Institute to study paediatric MS

    The Jacobs Neurological Institute of the University at Buffalo has received a $1.8 million, 5-year grant from the National Multiple Sclerosis Society to establish a paediatric multiple sclerosis center.

    To be located at Women & Children's Hospital of Buffalo, it will be one of six such centers to be created in the United States.

    The center will treat children under 18 years of age who have MS and other diseases of the central nervous system. The center also will function as a clinical and basic sciences research center on paediatric nervous system conditions and have an education mission to teach physicians and families about the symptoms and treatment options for children.

    MS commonly is perceived as an "adult disease" that affects young to middle-aged adults. However, diagnostic tools now reveal that as many as 10,000 children -- or about 5 percent of all those diagnosed -- in the country have MS. About 15,000 children may have symptoms of MS.

    Dr. Bianca Weinstock-Guttman,director of Jacobs' Baird MS Center and a UB associate professor of neurology, will be the director of the new center.

    "Many general paediatricians are not familiar with MS, particularly since they are not expecting to see it in children," said Weinstock-Guttman. "The Paediatric MS Center will provide comprehensive care and a wide range of services, including in-patient and out-patient neurological care, physical therapy and rehabilitation and family education in the child-friendly environment of Women & Children's Hospital."

    Western New York has one of highest rates of adult MS in the country, with approximately 160 diagnosed cases per 100,000 population, according to the Western New York/Northwestern Pennsylvania Chapter of the National Multiple Sclerosis Society. The national rate of diagnosed MS cases is approximately 50 per 100,000.

    The other regional paediatric MS centers are in Long Island, San Francisco, Alabama, Minnesota and Massachusetts.

    © 2006 American City Business Journals Inc (19/01/06)

    Thousands of Children Experiencing What May Be Symptoms of Multiple Sclerosis

    MS Not Just An 'Adult Disease'; First-Of-Its-Kind Network of Paediatric Multiple Sclerosis Centers of Excellence Established Nationwide(USA).

    Every hour in the United States, someone is diagnosed with multiple sclerosis, an unpredictable, often disabling disease of the central nervous system. While it's the most common neurological condition affecting young to middle-aged adults, emerging research suggests up to 10,000 children in the U.S. are living with the condition and another 15,000 have experienced MS-like symptoms such as double vision, numbness and unexplained fatigue.

    The National Multiple Sclerosis Society is establishing this first-ever network of Paediatric MS Centers of Excellence as part of its new $30 million promise 2010 initiative supporting important yet under-explored areas of MS research and patient care.

    Medical experts say one of the many challenges with paediatric MS is that it usually is not on a paediatrician's or a neurologist's radar screen when kids are reporting possible MS symptoms. These centers will give doctors the tools they need to help identify and treat MS early on.

    Source: The National Multiple Sclerosis Society (28/12/05)

    Glatiramer acetate (Copaxone) Safe For Paediatric Multiple Sclerosis: Presented at ECTRIMS
    Glatiramer acetate (Copaxone) treatment of children with multiple sclerosis is safe, with a safety profile similar to that found among adults, researchers reported here on September 29th at the 21st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

    "Children get multiple sclerosis, and we found in this study children can be treated with multiple sclerosis in the same way adults can be treated," said lead investigator Lauren Krupp, MD, Professor of Neurology and Director, National Paediatric Multiple Sclerosis Center, State University of New York Medical Center, Stony Brook, New York.. "We found that they can be treated equally safely with Copaxone, or glatiramer acetate."

    The investigators conducted a retrospective chart review of 16 girls and 11 boys with a mean age of 12.2 years at onset of relapsing remitting multiple sclerosis (RRMS) who were diagnosed at or before age 18 years. They included subjects from five North American sites.

    Subjects received off-label treatment with glatiramer acetate 20 mg/day, injected subcutaneously daily for a mean of 20.0 months (range, 2.0 to 60.0 months). Patients started glatiramer acetate treatment at mean age of 14.1 years and at a mean of 13.2 months post-diagnosis.

    Sixty-four adverse events were reported among 17 patients. Less than 6% of reported adverse events resulted in temporary or permanent discontinuation of therapy after a mean of 14.8 months on glatiramer acetate.

    Most frequently reported adverse events were comparable to the adult data, and they included injection site reactions in 8 patients (23.4%), skin reactions in 2 patients (12.5%), bronchitis in 4 patients (6.3%), and dyspnea in 3 patients (4.7%).

    There was no evidence of abnormal laboratory values or vital signs.

    "In summary," the authors wrote in their abstract, "[glatiramer acetate] was extremely well tolerated."

    The researchers calculated the annual relapse rate for the patients who had at least 12 and 24 months of pre- and post-treatment data. They observed a 56% decrease in the frequency of relapse in the first 12 months and a 58 % decrease in relapse frequency was seen for the smaller subset in the patients for whom 24-months post-treatment data was available.

    Dr. Krupp concluded, "This medication, which is safe in adults, is equally safe in children. The clinical implication is that it's safe, so use it."

    Presentation title: Safety and Tolerability of Copaxone(R) in Paediatric Patients With Relapsing-Remitting Multiple Sclerosis. Poster 332 (03/10/05)

    © Multiple Sclerosis Resource Centre (MSRC)

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