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Paediatric MS

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Children with MS have higher disease activity but better myelin repair than adults(14/04/14)

Quantitative determination of regional lesion volume and distribution in children and adults with RRMS.

Abstract

INTRODUCTION: Onset of MS occurs during childhood in about 5% of cases. It is unclear whether very young age at MS onset, when the nervous system is still myelinating, affects MS lesion accrual or regional distribution.

OBJECTIVE: To compare the frequency, volume and distribution of T2 and T1 lesions in children and adults with relapsing-remitting multiple sclerosis (RRMS).

METHODS: Lesions were segmented on T2- and T1-weighted MRI images from 29 children and 29 adults with RRMS, matched for disease duration.

RESULTS: All subjects exhibited T2-weighted brain lesions. Children had higher whole-brain T2-weighted-lesion-volume (T2LV) compared to adults (mean (SD) in cm(3): 12.76(2.7) vs. 10.03(3.4), p<0.0013). The supratentorial-T2LV was similar in children and adults (8.45(1.7) vs. 7.94(1.7), mean (SD), p?=?0.2582), but adults were more likely to have supratentorial lesions (96.5% vs. 68.9%, p<0.012). Children were more likely to have infratentorial-T2-weighted lesions (75.9% vs. 43.4%, p<0.03), specifically in the brainstem (62.1% vs. 26.7%, p<0.019) and the pons (48.3% vs. 17.24%, p<0.024), had higher infratentorial-T2-weighted-lesion counts (4.1(5.6) vs. 1.45(2.3), p<0.021), a greater infratentorial-T2LV (4.31(2.7) vs. 2.08(2.4), p<0.0013), and a greater infratentorial-T1-weighted-lesion-volume (T1LV) (3.7(2.5) vs. 1.08(1.9), p<0.0007). Whole-brain-T1LV was higher in children (9.3(2.5) vs. 6.43(2.1), p>0.001). Adult MS patients had higher supratentorial-T1LV (5.5(0.92) vs. 6.41(2.1), mean (SD), p<0.034), whereas children were more likely to have infratentorial-T1-weighted lesions (58.6% vs. 23.3%, p<0.015).

DISCUSSION: Onset of MS during childhood is associated with a higher volume of brain lesions in the first few years of disease relative to adults. Children with MS are more likely than adults to have T2 and T1 lesions in the infratentorial white matter, raising the possibility of preferential immune targeting of more mature myelin. Children with MS have a lower supratentorial T1 lesion burden, possibly reflecting more effective remyelination and repair in brain regions that are still engaged in active primary myelination.

Ghassemi R, Narayanan S, Banwell B, Sled JG, Shroff M, Arnold DL; Canadian Pediatric Demyelinating Disease Network.

Full Article  

Source: PLoS One. 2014 Feb 26;9(2):e85741. doi: 10.1371/journal.pone.0085741. eCollection 2014. & PMID: 24586244 (14/04/14)

Epstein-Barr virus in oral shedding of children with multiple sclerosis(30/10/13)

ABSTRACT

Objective: To investigate Epstein-Barr virus (EBV) oral shedding frequency and EBV genetic diversity in pediatric patients with multiple sclerosis (MS).

Methods: This was a prospective case-control study. We used PCR-based assays to detect viral DNA in the monthly mouth swabs of 22 pediatric patients with MS and 77 age- and sex-matched healthy controls. EBV-positive samples were further analyzed for sequence variation in the EBV BCRF1 (ebvIL-10) gene using direct DNA sequencing methods, and in the EBV LMP1 gene by mass spectrometry.

Results: Nineteen of the 22 (86.4%) children with MS were seropositive for remote EBV infection compared to 35 out of 77 (45.5%) healthy controls (p = 0.008). Baseline analysis of mouth swabs revealed a higher proportion of EBV-positive samples from EBV-seropositive patients with MS compared to EBV-seropositive healthy controls (52.6% vs 20%, p = 0.007). Longitudinal analysis of monthly swabs revealed average EBV detection rates of 50.6% in patients with MS and 20.4% in controls (p = 0.01). The oral shedding frequencies of Herpesviruses herpes simplex virus–1, cytomegalovirus, human herpesvirus (HHV)-6, and HHV-7 did not differ between groups. Changes in the predominant EBV genetic variants were detected more frequently in patients with MS; however, no specific EBV genetic variant was preferentially associated with MS.

Conclusion: Children with MS demonstrate abnormally increased rates of EBV viral reactivation and a broader range of genetic variants, suggesting a selective impairment in their immunologic control of EBV.

Carmen Yea, MSc, Raymond Tellier, MD, Patrick Chong, PhD, Garrett Westmacott, PhD, Ruth Ann Marrie, MD, PhD, Amit Bar-Or, MD, Brenda Banwell, MD; On behalf of the Canadian Pediatric Demyelinating Disease Network

Full Text 

Source: Neurology © 2013 American Academy of Neurology (30/10/13)

Safety and efficacy of mitoxantrone in pediatric patients with aggressive MS(28/10/13)

Abstract

OBJECTIVE: The purpose of this study was to assess the safety and efficacy of mitoxantrone (MX) in pediatric patients with aggressive multiple sclerosis (MS).

METHODS: A retrospective analysis on pediatric MS patients treated with MX was performed with regards to demographic/clinical parameters and magnetic resonance imaging (MRI) findings.

RESULTS: 19 definite pediatric MS cases with mean ± SD age of 15.4 ± 2.8 years underwent 20 mg MX for control of their severe/frequent relapses, high EDSS score or new and active brain MRI lesions. After a median [IQR] follow-up period of 30[12-60] months, 14 cases (73%) were relapse free; the EDSS score decreased by at least 0.5 in 16 cases (84.2%); and gadolinium-enhancing lesion volume fell by 84.2% in 16 cases. Adverse events included nausea and vomiting, fatigue, alopecia, palpitation, cardiomyopathy and mild leukopenia. All adverse events were mild and transient.

CONCLUSION: Our results suggest MX is a good candidate for treatment of children with worsening RRMS and SPMS. Recommendations regarding patient selection, treatment administration, and close follow-up should be considered. Continuing research is needed to establish its efficacy and safety profile in a multinational collaboration with careful follow-up of adverse events.

Etemadifar M, Afzali P, Abtahi SH, Ramagopalan SV, Nourian SM, Murray RT, Fereidan-Esfahani M.

Department of Neurology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran; Isfahan Research Committee of Multiple Sclerosis (IRCOMS), Isfahan University of Medical Sciences, Isfahan, Iran.

Sources: Eur J Paediatr Neurol. 2013 Oct 7. pii: S1090-3798(13)00131-1. doi: 10.1016/j.ejpn.2013.09.001. [Epub ahead of print] Copyright © 2013 European Paediatric Neurology Society & Pubmed PMID: 24139067 (28/10/13)

Childhood stress not a likely trigger for MS(07/10/13)

Stressful life events in childhood did not appear to increase the subsequent risk for multiple sclerosis (MS), researchers said here.

In large Danish cohort study, children who experienced stressful life events had a weak 1.11-fold risk (95% CI 1.02-1.20) of later developing MS compared to unexposed children, according to Nete Munk Nielsen, MD, PhD, from Statens Serum Institut in Copenhagen, and colleagues.

However, there was a "slightly increased risk of MS" for kids who experience parental divorce (relative risk 1.13, 95% CI 1.04-1.23) compared to children who did not, they wrote in their poster presentation at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting.

While stressful events are often associated with risk for MS in adults, studies that have looked for an association between stress and MS in children have turned in mixed results.

The authors pointed out that a recent study found that adults exposed to emotional or sexual abuse as children were at 2.2- to 3.4-fold increased risk of MS. However, another study reported no association between physical or sexual abuse in childhood and risk for MS.

The authors analyzed Danish public health records that included nearly 3 million individuals born between 1968 and 2011. The Danish Civil Registration System contains updated information on family relations, marital status, and vital statistics on every Danish person since April 1, 1968. The researchers compiled data on parental and sibling deaths as well as parental divorce. Information about cases of MS in the study cohort was obtained from the Danish MS Registry.

The cohort represented 63 million person-years of follow-up. The records showed that 15.8% of the population was exposed to at least one stressful life event before the age of 18, with most of those events being parental divorce.

The researchers identified 3,260 individuals in the cohort who were later diagnosed with MS.

The death of a parent had a nonsignificant 4% increased risk (95% CI 0.90-1.21) of a later MS diagnosis, while death of a sibling before age 18 had a similar nonsignificant 4% impact (95% CI 0.81-1.32).

"There have been conflicting studies over whether stressful events in a person's childhood leads to MS, but in our analysis, we did not find strong evidence for this," Nielsen said during her poster presentation.

"We cannot exclude a biological effect of stress on the susceptibility to MS, but do consider adoption of unhealthy behaviors more likely to explain our findings," she added.

That may be particularly true in the findings on parental divorce. Nielsen said that children's lives may be impacted by living with one parent with reduced income, resulting in less access to healthier lifestyles. Unhealthy lifestyles have been linked to a higher MS risk.

She added that her group will continue to research which life events may confer a risk for MS and disease development.

Nielsen reported no conflicts of interest. A co-author reported relationships with Biogen Idec, Novartis, and Teva.

Primary source: European Committee for Treatment and Research in Multiple Sclerosis

Source reference: Nielsen N, et al. "Stressful life-events in childhood and risk of multiple sclerosis" ECTRIMS 2013; Abstract P302.

Source: MedPage Today © 2013 MedPage Today, LLC (07/10/13)

MS risk rises with childhood Diabetes - study(30/09/13)

For young people, type 1 diabetes may raise the likelihood of having multiple sclerosis. Scientists now suspect that certain environmental factors may play a role.

Type 1 diabetes and multiple sclerosis (MS) are both autoimmune diseases, meaning a person's immune system causes damage to their own body.

Type 1 diabetes (sometimes called juvenile diabetes because it is usually diagnosed in childhood) is an autoimmune attack against the beta cells in the pancreas while, with multiple sclerosis, the immune system attacks the brain and spinal cord.

Recent research backed up previous studies which found that children and adolescents with diabetes face greater odds of getting MS. Investigators discovered that environmental factors, including when a person is born, may heighten this risk.

Susanne Bechtold, MD, in the Department of Pediatrics, Medical University Munich, Germany, and a team of researchers analyzed data on 56,653 children and adolescents with type 1 diabetes under the age of 21 from Germany and Austria.

The authors discovered 19 of these patients had MS.

Researchers compared MS prevalence rates from the Mid-European and German MS pediatric and adult registers with their data. They calculated an MS prevalence of 7 to 10 patients per 100,000 with type 1 diabetes, compared with 3 to 5 cases per 100,000 in a non-diabetes population.

The risk of the diabetes patients having MS was three to almost five times greater.

The investigators also cited three possible influencing factors that could be adding to the risk of developing MS—immigration status, thyroid antibodies (only in males) and month of birth.

There was a higher MS risk in patients with an immigrant background. The authors wrote "...we assume that variations in their genetic, environmental or cultural background caused this significantly increased risk to simultaneously develop type 1 diabetes and MS."

Male patients with thyroid specific antibodies also had a higher chance of developing MS. Thyroid antibodies are an immune response of the body, which is considered to be abnormal.

Also, researchers noted that among the diabetes-MS patients, dates of birth peaked in June and August.

Dr. Bechtold told dailyRx News, “We think that environmental factors might influence the immunological system, like by vitamin D level during early pregnancy. The theory regarding month of birth is that vitamin D has immune-modulating capacities.”

This study found that two-thirds of patients with type 1 diabetes and MS had a birth month consistent with the fetus having experienced lower levels of ultraviolet exposure during early pregnancy. Exposure to sunlight can be a source of vitamin D.

“Overall this is speculation and I am not aware on any study investigating the influence of different environmental factors in detail on the fetus,” said Dr. Bechtold.

The authors qualified their results, writing that the low number of MS patients did not reach statistical significance.

“In the next step, we are going to contact each of the 19 patients to get more detailed information of history, family history and immunological data,” Dr. Bechtold told dailyRx News. “Only with these hopefully more detailed knowledge we may give advice.”

The study was published online in September in Diabetes Care ahead of print.

Source: dailyRX © 2013 dailyRx, Inc (30/09/13)

The risks of childhood multiple sclerosis(04/09/13)

Abstract

OBJECTIVE: To evaluate the practical application of International Pediatrics Multiple Sclerosis study group definitions in children with inflammatory demyelination of the central nervous system and to identify predictors of multiple sclerosis.

METHODS:Baseline data on 123 children with a first episode of acute central nervous system demyelination were collected. The initial diagnosis according to the International Pediatrics Multiple Sclerosis study group was recorded and compared with final diagnosis.

RESULTS:Forty-seven (38.2%) children met International Pediatrics Multiple Sclerosis study group criteria for acute disseminated encephalomyelitis and 67 (54.4%) had clinically isolated syndrome at the initial presentation. Four (3.2%) had the diagnosis of neuromyelitis optica and five (4%) did not meet any specific diagnosis per the study group criteria. Clinical follow-up was available on 118 of 123 children (95.9%), with a median of 61.5 months (quartile range 23, 110 months). Conversion from clinically isolated syndrome to multiple sclerosis occurred in 26 of 67 children (38.8%); acute disseminated encephalomyelitis to multiple sclerosis occurred in 4 of 47 children (8.5%). Adjusted multivariate logistic regression analysis for an outcome of future development of multiple sclerosis showed the following predictors: female gender (odds ratio 12.44; 95% confidence interval 1.03-149.3); initial diagnosis of monofocal brain stem or hemispheric dysfunction (odds ratio 24.57; 95% confidence interval 3.06-196.78); and Callen magnetic resonance imaging criteria if met (odds ratio 122.45; 95% confidence interval 16.57-904.57).

CONCLUSION:International Pediatrics Multiple Sclerosis study group criteria affirm that children with initial clinically isolated syndrome are more likely to develop future multiple sclerosis compared with those with an acute disseminated encephalomyelitis initial diagnosis. In addition, female gender, brain stem or hemispheric involvement, and Callen magnetic resonance imaging criteria predict the diagnosis of multiple sclerosis.

Peche SS, Alshekhlee A, Kelly J, Lenox J, Mar S.A Long-Term Follow-Up Study Using IPMSSG Criteria in Children With CNS Demyelination.

Sources: Pediatr Neurol. 2013 Aug 27. doi:pii: S0887-8994(13)00401-3. 10.1016/j.pediatrneurol.2013.06.023& Pubmed PMID: 23993834 (04/09/13)

Elevated relapse rates in paediatric compared to adult MS persist for at least 6 years(25/07/13)

Abstract

Objective
To compare relapse rates in paediatric-onset multiple sclerosis (POMS) and adult-onset multiple sclerosis (AOMS) over the first 6-years of disease.

Methods
Patients with relapsing-remitting disease onset were identified from the Partners Pediatric MS Center, Massachusetts General Hospital and Partners MS Center, Brigham and Women's Hospital. 84 POMS and 258 AOMS patients were included. Annualized relapse rates (ARR) for each individual year from year 1 to year 6, after first attack were compared using Poisson regression, as was expanded disability status scale (EDSS) score at the visit closest to each year interval.

Results
ARR was significantly higher in POMS compared to AOMS at individual years (except year 4), and was not significantly affected by adjustment for gender, race and proportion of time on treatment. Despite a 2.30 times higher relapse rate over 6-years, EDSS between groups did not differ. ARR in years 1–5 did not impact year 5 disability measured by EDSS in POMS.

Conclusions
Our findings demonstrate that higher ARR in POMS relative to AOMS is sustained over 6-years, suggesting a more inflammatory nature and potential disconnect between relapses and disability measured by EDSS early in POMS. This data may be useful when designing clinical trials for POMS.

L.A. Benson, B.C. Healy, M.P. Gorman, N.F. Baruch, T. Gholipour, A. Musallam, T. Chitnis. Source: Multiple Sclerosis and Related Disorders © 2013 Elsevier B.V. (25/07/13)

Tysabri may be an option for children with Multiple Sclerosis(20/02/13)

Off-label treatment with natalizumab (Tysabri) for 20 children with severe multiple sclerosis reduced relapses and brain lesions seen on MRI scans, a retrospective analysis found.

The mean annualized relapse rate while on natalizumab in these patients was 0.4, compared with 3.77 before starting the drug (P<0.001), according to Barbara Kornek, MD, of Austria's Medical University of Vienna, and colleagues.

Also, new T2/fluid attenuated inversion recovery (FLAIR) lesions declined from a mean of 7.8 before natalizumab to 0.5 on the drug (P=0.001), the researchers reported online in JAMA Neurology.

But the treatment was not without adverse events, Kornek and colleagues noted. Half the patients experienced some type of clinical event, including one case each of severe asthenia, laryngeal edema, and anaphylaxis. Two had recurrent infections, although it was not clear that natalizumab was responsible.

Eight of the children also exhibited laboratory abnormalities. Four developed mild anemia, two showed transient elevations in liver enzymes, and two developed hyperbilirubinemia.

In addition, two patients developed high levels of neutralizing antibodies to natalizumab that led to withdrawal of the drug. Three other patients stopped natalizumab after tests showed the presence of antibodies to the JC virus, a strong risk factor for development of progressive multifocal leukoencephalopathy (PML), which can be fatal.

One patient had tested positive for JC virus antibodies before starting natalizumab, but the decision was made to use the drug anyway because of a "highly active disease course." Overall, the researchers found, five of 13 patients tested for JC virus antibodies were positive.

Natalizumab is not currently approved for pediatric use in the U.S. or Europe, but it is sometimes used anyway in children with very severe disease or who do not respond to more conventional disease-modifying treatments.

The 20 children Kornek and colleagues reported on were mostly teenagers and were receiving the drug in 11 clinics in Germany and Austria. In addition to the standard outcomes of relapse rates and MRI lesions, the researchers paid particular attention to development of neutralizing anti-drug antibodies and JC virus antibody status, as these had not previously been studied in a pediatric population.

Mean age at disease onset in these patients was 15.2 (SD 1.3) and the mean age when natalizumab was started was 16.7 (SD 1.1). All but four were girls.

One patient started on natalizumab as first-line treatment, 15 had previously received one disease-modifying treatment, and four had received two.

With a mean of 18 months of disease duration before starting natalizumab, the average number of relapses was 4.3, with 3.1 occurring in the previous year -- numbers that signify highly active disease.

Four of the patients had undergone plasma exchange for a severe, prolonged relapse event.

The mean number of T2/FLAIR brain lesions at pre-natalizumab baseline was 30 (SD 17), with a mean of 2 gadolinium-enhancing lesions.

Mean treatment duration for natalizumab in the analysis was 20 months, during which time 14 of the 20 patients remained relapse-free. Among seven patients on the drug for 2 years or more, four stayed relapse-free.

Only two patients did not show a significant reduction in relapse frequency with natalizumab.

In an analysis combining clinical and MRI results, six of 13 patients with adequate data were deemed to be free of disease activity with natalizumab, insofar as they had no relapses, did not develop new MRI lesions, or show disability progression.

Among 10 patients with complete data for at least 1 year, four were disease-free throughout follow-up.

Most of the patients actually showed some lessening of disability, with a median change in EDSS score of -0.25 points (interquartile range -1.25 to 0.00) relative to baseline, when the group median was 2.0 points.

Kornek and colleagues also looked at the clinical course of patients who had stopped natalizumab either permanently or temporarily. After excluding two who were lost to follow-up after stopping the drug and one who had stopped temporarily during pregnancy, there were nine patients available for this analysis, including eight followed for at least 6 months.

Among those eight, six developed relapses in the first 6 months off natalizumab. The annualized relapse rate among all nine patients showed a strong trend toward increase (mean difference 1.47, 95% CI -0.04 to 2.98, P=0.06).

Overall, Kornek and colleagues concluded that natalizumab "may be safe and effective against MS in pediatric patients with breakthrough disease," but they cautioned that controlled trials are needed to confirm a favourable benefit-risk balance.

The study had no external funding.

Study authors reported relationships with Biogen Idec, Merck Serono, Teva, Bayer Schering, Novartis, Sanofi, UCB, Orion, Solvay, Mundipharma, and Ipsen.

Primary source: JAMA Neurology
Source reference: Kornek B, et al "Natalizumab therapy for highly active pediatric multiple sclerosis" JAMA Neurol 2013; DOI: 10.1001/jamaneurol.2013.923.

Source: MedPage Today © 2013 MedPage Today, LLC. (20/02/13)

Natalizumab in paediatric multiple sclerosis: results of a cohort of 55 cases(15/02/13)

Abstract

BACKGROUND: Limited information is available on the use of natalizumab (NA) in pediatric multiple sclerosis (ped-MS) patients.

OBJECTIVE: The purpose of this study was to describe the long-term effects of NA in a large cohort of active ped-MS patients.

METHODS: Patients with definite ped-MS were treated with NA if in the previous year they had experienced at least two relapses or a severe relapse with incomplete recovery while on immunomodulating treatment, or at least two relapses and new magnetic resonance imaging (MRI) lesions regardless of any prior treatment.

RESULTS: The study included 55 patients (mean age: 14.4 years, mean number of relapses: 4.4, pre-treatment mean disease duration: 25.5 months). They received a median number of 26 infusions. Three relapses occurred during the follow-up, one female patient continued to deteriorate in cognitive functioning. Mean Expanded Disability Status Scale (EDSS) scores decreased from 2.7 to 1.9 at the last visit (p<0.001). During the follow-up the majority of patients remained free from MRI activity. Transient and mild clinical adverse events occurred in 20 patients. Mild hematological abnormalities occurred in seven patients. Anti-JCV antibodies were detected in 20/51 tested patients.

CONCLUSIONS: NA was well tolerated in all patients. A strong suppression of disease activity was observed in the majority of patients during the follow-up.

Ghezzi A, Pozzilli C, Grimaldi L, Moiola L, Brescia-Morra V, Lugaresi A, Lus G, Rinaldi F, Rocca M, Trojano M, Bianchi A, Comi G, Filippi M; the Italian MS Study Group.

Source: Mult Scler. 2013 Feb 11 & Pubmed PMID: 23401129 (15/02/13)

One in Three Children with MS has Cognitive Impairment(06/02/13)

Data from the largest multicenter study accessing cognitive functioning in children with multiple sclerosis (MS) reveals that one-third of these patients have cognitive impairment, according to a research paper published in the Journal of Child Neurology. Led by Lauren B. Krupp, MD, Director of the Lourie Center for Pediatric Multiple Sclerosis at Stony Brook Long Island Children’s Hospital, the study indicates that patients experience a range of problems related to cognition.

In “Cognitive Impairment Occurs in Children and Adolescents with Multiple Sclerosis: Results from a United States Network,” Dr. Krupp and colleagues from Stony Brook and five other national Pediatric MS Centers of Excellence measured the cognitive functioning of 187 children and adolescents with MS, and 44 who experienced their first neurologic episode (clinically isolated syndrome) indicative of MS. They found that 35 percent of the patients with MS and 18 percent of those with clinically isolated syndrome met criteria for cognitive impairment. All patients were under age 18 with an average disease duration of about two years.

“This study is important because it represents the largest study to date to apply a comprehensive neuropsychological battery of tests to evaluate the cognitive functioning of children with MS, and the results clearly show us that cognitive issues are widespread and can occur early on in the disease course of these patients,” said Dr. Krupp, also a Professor of Neurology at Stony Brook University School of Medicine. “These are critically important findings that emphasize the need for prompt recognition of our patients’ cognitive problems and for neurologists and other MS specialists to discover ways to intervene and help improve the cognitive abilities of these children while they are in school and beyond.”

The authors report that the network of Pediatric MS Centers of Excellence used a comprehensive battery of 11 tests where the scores addressed cognitive domains such as general ability, reading and language, attention, working memory and speed processing, executive functioning, verbal learning and recall, visual-motor integration, and fine motor speed and coordination. The testing took approximately 2.5 hours to complete, and a participant was considered impaired when the proportion of impaired scores from the categorized tests was greater than one-third.

They found that the most frequent areas of impairment were fine motor coordination (54 percent), visual-motor integration (50 percent), and speeded information processing (35 percent). Among the various tests that showed the most frequent rate of impairment were the grooved peg board, a measure of fine motor speed and coordination, and a test for visual-motor integration, a measure that is dependent in part on fine motor coordination.

The researchers factored in clinical variables in the analysis, including disease duration, diagnosis status, age of disease onset, and disability. They found that a diagnosis of MS and overall neurologic disability were the only two independent predictors of cognitive impairment.

They also factored in sociodemographic variables such as age, gender and ethnicity, and leveraged the geographic diversity of the Pediatric Multiple Sclerosis Centers of Excellence network to create the sample. Centers participating in the study included: the Lourie Center for Pediatric Multiple Sclerosis at Stony Brook; the University of California, San Francisco; University of Alabama, Birmingham; the Jacobs Neurological Institute, SUNY Buffalo; Massachusetts General Hospital in Boston, and the Mayo Clinic in Rochester, Minn.

The authors point out that the next step for pediatric MS investigators within the network is to further the research “to develop strategies for prompt identification of children with multiple sclerosis at risk for cognitive problems so that treatment can be initiated.”

The study was supported in part by the National Multiple Sclerosis Society.

About the Lourie Center for Pediatric Multiple Sclerosis
The Lourie Center for Pediatric Multiple Sclerosis, part of Stony Brook Long Island Children’s Hospital, was established to advance the recognition, evaluation, and treatment of children and adolescents with MS through the creation of a multidisciplinary program dedicated to clinical care and scientific research of children and adolescents with MS. The Center includes a team of clinical experts in MS, pediatric neurology, nursing, social work, psychiatry, neuroimaging, and neuropsychology. Collaborating with clinicians are researchers from a variety of fields including neuroscience, neuroimmunology, genetics, physics, and chemistry. The center has been designated a Center of Excellence by the National Multiple Sclerosis Society.

Source: Newswire ©2013 Newswise, Inc (06/02/13)

Obese girls at risk of multiple sclerosis, study finds(31/01/13)

Obese girls are at greater risk of developing multiple sclerosis or MS-like illness, according to a new study published Wednesday in the online journal Neurology.

Researchers looked at body mass index (BMI) data from more than 900,000 children from the Kaiser Permanente Southern California Children's health study. Seventy-five of those children and adolescents between the ages of 2 and 18 were diagnosed with pediatric MS. More than 50% of them were overweight or obese, and the majority were girls.

According to the study, the MS risk was more than one and a half times higher for overweight girls, almost two times higher in moderately obese girls and almost four times higher in extremely obese girls.

"Over the last 30 years, childhood obesity has tripled," said study author Dr. Annette Langer-Gould, a neurologist and regional MS expert for Kaiser Permanente in Southern California. "In our study, the risk of pediatric MS was highest among moderately and extremely obese teenage girls, suggesting that the rate of pediatric MS cases is likely to increase as the childhood obesity epidemic continues."

MS is a chronic, debilitating disease that attacks the central nervous system. "Some patients do very well and have minimal to no disability even 20 years later," Langer-Gould said, "While other patients do poorly and can be wheelchair bound in 5 years. It's a huge spectrum."

Dr. Tanuja Chitnis is a neurologist and pediatric MS specialist at Massachusetts General Hospital for Children with 50 MS publications to her credit. She says 10 years ago MS was not recognized as a disease that occurred in children, but today evidence is mounting that obesity is a risk factor for MS in kids, particularly adolescent girls.

"This is one more piece of evidence, but really in order to make a definitive link, you need at least five or six studies showing the same thing," she says. "You need to have an underlying biological reason, which still has not been worked out and you need to show that blocking or interfering with the biological mechanism can prevent the disease."

"The overall message is that there are an increasing number of diseases associated with obesity and particularly early obesity and that it's an important risk factor to try to mitigate. It is something you can do something about," Chitnis says.

According to the Centers for Disease Control and Prevention, over the last 30 years childhood obesity has doubled in children and tripled in teenagers. In 2010, more than a third of all children and teens were overweight or obese.

At Children's Hospital of Alabama, pediatric neurologist Dr. Jayne Ness has seen more than 100 pediatric MS patients, predominantly girls, whose average age at onset is 13. Ness told CNN she has noticed a rise in obesity in their MS patients, kids who at the time of diagnosis are obese.

"Does this mean that obesity is a risk factor for MS? We don't know yet," Ness said. "It's one more piece that helps us potentially better understand some of the underlying triggers of pediatric MS and may help us understand MS in general."

Langer-Gould says that while pediatric MS is very rare - only 1.6 per 100,000 children - there are red flags parents should look out for. "Constant numbness or tingling from the waist down or numbness, pins and needles sensations in the chest, abdomen or back that last for 24 hours."

Those children should be evaluated by a neurologist. Other symptoms to have checked out are collapsing weakness in the legs after modest exertion, and pain and loss of vision in one eye.

The National MS Society estimates about 10,000 children in the United States have the disease and another 10 to 15,000 have had at least one MS-like symptom. An estimated 5% of all MS cases worldwide are childhood or adolescent onset.

Source: CNN © 2013 Cable News Network.(31/01/13)

Fatigue, emotional functioning, and executive dysfunction in pediatric MS.(14/12/12)

Abstract

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(08/08/12)

Summary: 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.

Abstract

BACKGROUND AND PURPOSE:
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.

MATERIALS AND METHODS:
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.

RESULTS:
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).

CONCLUSIONS:
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)