Brenda Banwell

The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

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Publications (131)686.75 Total impact

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    ABSTRACT: Autoantibodies targeting conformationally intact myelin oligodendrocyte glycoprotein (MOG) are found in different inflammatory diseases of the CNS, but their antigenic epitopes have not been mapped. We expressed mutants of MOG on human HeLa cells and analyzed sera from 111 patients (104 children, 7 adults) who recognized cell-bound human MOG, but had different diseases, including acute disseminated encephalomyelitis (ADEM), one episode of transverse myelitis or optic neuritis, multiple sclerosis (MS), anti-aquaporin-4 (AQP4)-negative neuromyelitis optica (NMO), and chronic relapsing inflammatory optic neuritis (CRION). We obtained insight into the recognition of epitopes in 98 patients. All epitopes identified were located at loops connecting the β strands of MOG. The most frequently recognized MOG epitope was revealed by the P42S mutation positioned in the CC'-loop. Overall, we distinguished seven epitope patterns, including the one mainly recognized by mouse mAbs. In half of the patients, the anti-MOG response was directed to a single epitope. The epitope specificity was not linked to certain disease entities. Longitudinal analysis of 11 patients for up to 5 y indicated constant epitope recognition without evidence for intramolecular epitope spreading. Patients who rapidly lost their anti-MOG IgG still generated a long-lasting IgG response to vaccines, indicating that their loss of anti-MOG reactivity did not reflect a general lack of capacity for long-standing IgG responses. The majority of human anti-MOG Abs did not recognize rodent MOG, which has implications for animal studies. Our findings might assist in future detection of potential mimotopes and pave the way to Ag-specific depletion.
    The Journal of Immunology 09/2013; · 5.52 Impact Factor
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    ABSTRACT: Background: There has been tremendous growth in research in pediatric multiple sclerosis (MS) and immune mediated central nervous system demyelinating disorders since operational definitions for these conditions were first proposed in 2007. Further, the International Pediatric Multiple Sclerosis Study Group (IPMSSG), which proposed the criteria, has expanded substantially in membership and in its international scope.
    Multiple Sclerosis 09/2013; 19(10):1261-1267. · 4.47 Impact Factor
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    ABSTRACT: To estimate sample sizes for pediatric multiple sclerosis (MS) trials using new T2 lesion count, annualized relapse rate (ARR), and time to first relapse (TTFR) endpoints. Poisson and negative binomial models were fit to new T2 lesion and relapse count data, and negative binomial time-to-event and exponential models were fit to TTFR data of 42 children with MS enrolled in a national prospective cohort study. Simulations were performed by resampling from the best-fitting model of new T2 lesion count, number of relapses, or TTFR, under various assumptions of the effect size, trial duration, and model parameters. Assuming a 50% reduction in new T2 lesions over 6 months, 90 patients/arm are required, whereas 165 patients/arm are required for a 40% treatment effect. Sample sizes for 2-year trials using relapse-related endpoints are lower than that for 1-year trials. For 2-year trials and a conservative assumption of overdispersion (ϑ), sample sizes range from 70 patients/arm (using ARR) to 105 patients/arm (TTFR) for a 50% reduction in relapses, and 230 patients/arm (ARR) to 365 patients/arm (TTFR) for a 30% relapse reduction. Assuming a less conservative ϑ, 2-year trials using ARR require 45 patients/arm (60 patients/arm for TTFR) for a 50% reduction in relapses and 145 patients/arm (200 patients/arm for TTFR) for a 30% reduction. Six-month phase II trials using new T2 lesion count as an endpoint are feasible in the pediatric MS population; however, trials powered on ARR or TTFR will need to be 2 years in duration and will require multicentered collaboration.
    Neurology 08/2013; · 8.25 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE:Chronic cerebrospinal venous insufficiency is a postulated etiologic factor for multiple sclerosis, but the higher frequency with longer disease duration and progressive disability suggests that chronic cerebrospinal venous insufficiency is secondary to chronic disease. We evaluated the presence of chronic cerebrospinal venous insufficiency in pediatric-onset MS.MATERIALS AND METHODS:Twenty-six pediatric patients with MS (18 years of age or younger), 26 age-matched healthy controls, and 13 young adults with pediatric-onset MS underwent sonography of the internal jugular, vertebral, and deep cerebral veins. Five venous hemodynamic criteria were assessed, with 2 criteria required for chronic cerebrospinal venous insufficiency. MR imaging studies, performed in the pediatric patients with MS and healthy control groups, included intracranial 2D time-of-flight MR venography and velocity-sensitive phase-contrast sequences. Contrast-enhanced brain MR images were obtained in pediatric patients with MS to further evaluate venous patency. We used paired t tests, Wilcoxon matched pairs, McNemar tests, and exact conditional logistic regression to estimate the association of chronic cerebrospinal venous insufficiency with MS.RESULTS:Fifty participants (73.5%) had normal ultrasound findings, 15 (23.1%) met 1 venous hemodynamic criterion, and 2 pediatric patients with MS and 1 young adult with pediatric-onset MS met chronic cerebrospinal venous insufficiency criteria. Chronic cerebrospinal venous insufficiency was not associated with MS (odds ratio, 2.41; 95% CI, 0.19-infinity). Demographic and disease characteristics did not differ between the patients with MS meeting chronic cerebrospinal venous insufficiency criteria (n = 3) and those who did not (n = 36; all, P > .05). The mean (SD) MR imaging measures of intracerebral flow did not differ between the 2 pediatric patients with MS meeting chronic cerebrospinal venous insufficiency criteria (0.85 ± 0.11) and healthy controls (0.87 ± 0.16, P = .50); no child demonstrated venous obstruction.CONCLUSIONS:Chronic cerebrospinal venous insufficiency is rarely observed in children or young adults with pediatric-onset MS. Venous anatomy and flow rates indicate that venous outflow is intact in pediatric patients with MS. Our findings argue against chronic cerebrospinal venous insufficiency as a component of MS etiology.
    American Journal of Neuroradiology 07/2013; · 3.17 Impact Factor
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    ABSTRACT: Background In a recent Canadian prospective study of children with acute demyelinating syndromes (ADS), we demonstrated that the presence of T2 periventricular and T1-hypointense lesions predicted MS diagnosis. We aimed to validate these predictors in a Dutch cohort of children with ADS.Methods Participants with ADS were identified from a prospective cohort or archived dataset. MS was diagnosed based on clinical or MRI evidence of relapsing disease. Baseline MRI scans were evaluated for the presence of the two predictive parameters. Sensitivity, specificity, positive (LR+) and negative likelihood ratios (LR−), and positive (PPV) and negative predictive value (NPV) were calculated to evaluate the performance of the MRI parameters at classifying children as having MS or monophasic demyelination.FindingsOf 115 children identified with ADS between December 1993 and December 2009, MRI scans from 87 children (45 prospective; 47 archived) were evaluated; scans of 28 children were excluded due to incomplete or poor quality imaging. Mean duration of observation was longer in the archived group (7.1 years, SD 3.5) than the prospective cohort (3.3 years, SD 1.4). 30 children were diagnosed with MS. Performance of the parameters was not statistically different between the prospective cohort (sensitivity 93.3% [68.1–99.8]; specificity 86.7% [69.3–96.2]; LR+ 7.0 [2.8–17.6]; LR− 0.08 [0.01–0.5]; PPV 77.8% [52.4–93.6]; NPV 96.3% [81.0–99.9]) and archived group (sensitivity 66.7% [38.4–88.2]; specificity 85.2% [66.3–95.8]; LR+ 4.5 [1.7–11.9]; LR− 0.4 [0.2–0.8]; PPV 71.4% [41.9–91.6]; NPV 82.1% [63.1–93.9]).InterpretationIn an independent Dutch cohort, we confirm that the presence of ≥1 T2 periventricular and ≥1 T1-hypointense lesions reliably identifies children with MS.FundingDutch MS Research Foundation.
    Multiple Sclerosis and Related Disorders. 07/2013; 2(3):193–199.
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    ABSTRACT: We describe the clinical and genetic features of a well-characterized cohort of patients with autosomal recessive hereditary spastic paraplegia (ARHSP) in the province of Ontario. Patients with documented corticospinal tract abnormalities were screened by whole gene sequencing and multiplex ligation probe amplification for mutations in nine genes known to cause ARHSP. Of a cohort of 39 patients, a genetic diagnosis was established in 17 (44 %) and heterozygous mutations were detected in 8 (21 %). Mutations were most frequent in SPG7 (12 patients), followed by SPG11 (10 patients), PNPLA6 (SPG39, 2 patients), and ZFYVE26 (SPG15, 2 patients). Although there are associations between some clinical manifestations of ARHSP and specific genes, many patients are tested at an early stage of the disease when phenotype/genotype correlations are not obvious. Accurate molecular characterization of well-phenotyped cohorts of patients will be essential to establishing the natural history of these rare degenerative disorders to enable future clinical trials.
    Neurogenetics 06/2013; · 3.58 Impact Factor
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    ABSTRACT: To expand current knowledge, we examined the safety and tolerability of subcutaneous interferon β-1a in patients with pediatric-onset multiple sclerosis. Records from 307 patients who had received at least 1 injection of subcutaneous interferon β-1a for demyelinating events when aged younger than 18 years were reviewed. Overall, 168 (54.7%) patients had at least 1 prespecified medical event related to or under close monitoring with subcutaneous interferon β-1a or specific to pediatric patients, 184 (59.9%) had nonserious medical events related to treatment or of unknown causality, and 12 (3.9%) had serious medical events irrespective of causality. The most common laboratory abnormalities were increased alanine (74/195; 37.9%) and aspartate aminotransferase levels (59/194; 30.4%). Annualized relapse rates were 1.79 before treatment and 0.47 during treatment. In conclusion, adult doses of subcutaneous interferon β-1a (44 and 22 μg, 3 times weekly) were well tolerated in pediatric patients and were associated with reduced relapse rates.
    Journal of child neurology 05/2013; · 1.59 Impact Factor
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    ABSTRACT: Magnetic resonance (MR) imaging is one of the most important paraclinical tools for the diagnosis of multiple sclerosis (MS), and monitoring of disease progression and treatment response. This article provides clinicians and neuroradiologists caring for children with demyelinating disorders with a suggested standard MR imaging acquisition and reporting protocol, and defines a standard lexicon for lesion features typical of MS in children. As there is considerable overlap between the MR imaging features of pediatric- and adult-onset MS, the recommendations provided herein may be of relevance to radiologists and clinicians caring for adults with multiple sclerosis.
    Neuroimaging Clinics of North America 05/2013; 23(2):217-226.e7. · 1.20 Impact Factor
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    ABSTRACT: Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disorder typically characterized by attacks of recurrent optic neuritis and transverse myelitis. Advances in magnetic resonance imaging techniques and the discovery of the relatively specific NMO IgG biomarker have led to improved diagnostic accuracy and greater recognition of the broad clinical spectrum of aquaporin 4-related autoimmunity. Brain lesions in NMO typically follow the distribution of aquaporin 4 expression and may be symptomatic. Prompt diagnosis of NMO and NMO spectrum disorders has important therapeutic implications given the high risk of recurrent attacks and consequent severe disability, especially in childhood-onset disease.
    Neuroimaging Clinics of North America 05/2013; 23(2):279-91. · 1.20 Impact Factor
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    ABSTRACT: The Canadian Multiple Sclerosis Working Group (CMSWG) developed practical recommendations in 2004 to assist clinicians in optimizing the use of disease-modifying therapies (DMT) in patients with relapsing multiple sclerosis. The CMSWG convened to review how disease activity is assessed, propose a more current approach for assessing suboptimal response, and to suggest a scheme for switching or escalating treatment. Practical criteria for relapses, Expanded Disability Status Scale (EDSS) progression and MRI were developed to classify the clinical level of concern as Low, Medium and High. The group concluded that a change in treatment may be considered in any RRMS patient if there is a high level of concern in any one domain (relapses, progression or MRI), a medium level of concern in any two domains, or a low level of concern in all three domains. These recommendations for assessing treatment response should assist clinicians in making more rational choices in their management of relapsing MS patients.
    The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 05/2013; 40(3):307-23. · 1.33 Impact Factor
  • Julia O'Mahony, Manohar Shroff, Brenda Banwell
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    ABSTRACT: This article reviews the features that should prompt consideration of diseases that mimic acquired demyelinating syndromes and multiple sclerosis using vignettes to highlight unusual clinical and radiologic features. Cases of transverse myelitis, spinal infarction, acute disseminated encephalomyelitis, fever-induced refractory epileptic encephalopathy in school-aged children, small-vessel vasculitis, Griscelli syndrome type 2, cysticercosis, vitamin B12 deficiency, and chronic relapsing inflammatory optic neuropathy are presented.
    Neuroimaging Clinics of North America 05/2013; 23(2):321-36. · 1.20 Impact Factor
  • Leonard H Verhey, Manohar Shroff, Brenda Banwell
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    ABSTRACT: In this article, the pathobiological, clinical, and treatment aspects of pediatric-onset multiple sclerosis (MS) are summarized, and the conventional magnetic resonance (MR) imaging (ie, T1-weighted, proton-density, and T2-weighted imaging) features of MS in children are discussed, as well as the application of MR imaging in the diagnosis of pediatric-onset MS and in prediction of MS in children with an incident central nervous system demyelination. Insights gained from studies comparing MR imaging features of pediatric-onset and adult-onset MS are presented.
    Neuroimaging Clinics of North America 05/2013; 23(2):227-43. · 1.20 Impact Factor
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    ABSTRACT: The 2010 McDonald criteria allow the diagnosis of multiple sclerosis (MS) at first attack in children and adults provided that the first attack symptoms are typical of MS and that the magnetic resonance imaging (MRI) conforms to prescribed features. We evaluate whether meeting the 2010 McDonald criteria at onset correlates with a more aggressive clinical course in a cohort of pediatric MS patients. The Expanded Disability Status Scale (EDSS) and annualized relapse rate were not associated with positivity for 2010 McDonald criteria at onset. The 2010 McDonald criteria identify children with similar MS features to those identified by clinical or MRI evidence of dissemination over time.
    Multiple Sclerosis 04/2013; · 4.47 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVE: Acute disseminated encephalomyelitis (ADEM) and relapsing-remitting multiple sclerosis (RRMS) share overlapping clinical, radiologic and laboratory features at onset. Because autoantibodies may contribute to the pathogenesis of both diseases, we sought to identify autoantibody biomarkers that are capable of distinguishing them. METHODS: We used custom antigen arrays to profile anti-myelin-peptide autoantibodies in sera derived from individuals with pediatric ADEM (n = 15), pediatric multiple sclerosis (Ped MS; n = 11) and adult MS (n = 15). Using isotype-specific secondary antibodies, we profiled both IgG and IgM reactivities. We used Statistical Analysis of Microarrays software to confirm the differences in autoantibody reactivity profiles between ADEM and MS samples. We used Prediction Analysis of Microarrays software to generate and validate prediction algorithms, based on the autoantibody reactivity profiles. RESULTS: ADEM was characterized by IgG autoantibodies targeting epitopes derived from myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein, and alpha-B-crystallin. In contrast, MS was characterized by IgM autoantibodies targeting myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein and oligodendrocyte-specific protein. We generated and validated prediction algorithms that distinguish ADEM serum (sensitivity 62-86%; specificity 56-79%) from MS serum (sensitivity 40-87%; specificity 62-86%) on the basis of combined IgG and IgM anti-myelin autoantibody reactivity to a small number of myelin peptides. CONCLUSIONS: Combined profiles of serum IgG and IgM autoantibodies identified myelin antigens that may be useful for distinguishing MS from ADEM. Further studies are required to establish clinical utility. Further biological assays are required to delineate the pathogenic potential of these antibodies.
    Multiple Sclerosis 04/2013; · 4.47 Impact Factor
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    ABSTRACT: OBJECTIVE: Pediatric studies for new biological agents are mandated by recent legislation, necessitating careful thought to evaluation of emerging multiple sclerosis (MS) therapies in children with MS. Challenges include a small patient population, the lack of prior randomized clinical trials, and ethical concerns. The goal of this meeting was to assess areas of consensus regarding clinical trial design and outcome measures among academic experts involved in pediatric MS care and research. METHODS: The Steering Committee of the International Pediatric MS Study Group identified key focus areas for discussion. A total of 69 meeting attendees were assembled, including 35 academic experts. Regulatory and pharmaceutical representatives also attended, and provided input, which informed academic expert consensus decisions. RESULTS: The academic experts agreed that clinical trials were necessary in pediatric MS to obtain pharmacokinetic, safety and efficacy data, and regulatory approval allowing for greater medication access. The academic experts agreed that relapse was an appropriate primary outcome measure for phase III pediatric trials. An international standardized cognitive battery was identified. The pros and cons of various trial designs were discussed. Guidelines surrounding MRI studies, pharmacokinetics, pharmacodynamics, and registries were developed. The academic experts agreed that given the limited subject pool, a stepwise approach to the launch of clinical trials for the most promising medications is necessary in order to ensure study completion. Alternative approaches could result in unethical exposure of patients to trial conditions without gaining knowledge. CONCLUSION: Consensus points for conduct of clinical trials in the rare disease pediatric MS were identified amongst a panel of academic experts, informed by regulatory and industry stakeholders.
    Neurology 03/2013; 80(12):1161-1168. · 8.25 Impact Factor
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    ABSTRACT: Objective: Cognitive impairment is a core symptom of pediatric-onset multiple sclerosis (MS), although relatively little is known regarding the rate of cognitive decline. This study examined the extent, pattern, and correlates of change in cognitive functioning in youth with MS. Method: Changes in cognitive performance in 28 patients with pediatric-onset MS and 26 age-matched controls were ascertained through repeat comprehensive neuropsychological assessment conducted over a 1-year period. Change was evaluated by using a mixed factorial design with repeated measures to determine the interaction between group and time and using the Reliable Change Index (RCI) to determine individual differences on test scores over time. Participants were classified as showing "decline" or "improvement" if change scores exceeded the RCI on three or more tests. Results: The pattern of change over time differed by group. At the group level, healthy controls were more likely to show improvement across multiple domains of function relative to the MS group. Using the RCI, 7 of 28 patients (25%) showed cognitive deterioration compared with only 1 of 26 controls (3.8%; p < .05). Performance on measures of attention and processing speed, visuomotor integration, verbal fluency, visual memory, and calculation and spelling ability were most responsive to deterioration in functioning over time. Longer disease duration was associated with greater deterioration in visuomotor integration. Increased lesion volume was associated with slower psychomotor speed over time. Conclusion: Lower rates of improvement in the pediatric MS group may be suggestive of a lack of age-appropriate cognitive development and warrant further evaluation over time. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
    Neuropsychology 03/2013; 27(2):210-9. · 3.58 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE:The degree to which MR imaging is useful in the diagnosis of MS is predicated on standardized and reliable evaluation of MR imaging parameters. We aimed to devise items for an MR imaging scoring tool that would have high inter-rater agreement and would be straightforward to apply.MATERIALS AND METHODS:On the basis of a literature search and consensus of an expert panel, we identified 48 parameters that describe acute CNS demyelination, predict MS diagnosis, or characterize demyelinating disorder mimics. MR images of children with clinically confirmed MS, monophasic ADEM, and angiography-negative biopsy-positive small-vessel primary angiitis of the CNS were scored by 2 neuroradiologists independently, using the preliminary 48-parameter tool. Parameters with Cohen κ ≥ 0.6 and deemed important in predicting diagnosis were retained. Parameters not visualized on routine clinical imaging or not important in differentiating MS, ADEM, and SV-cPACNS were discarded.RESULTS:Of 65 eligible patients, 55 children were enrolled (16 with monophasic ADEM, 27 with MS, 12 with SV-cPACNS); 10 were excluded (6 had hard-copy films, 4 did not meet MR imaging quality requirements). Of the 48 parameters, 16 were retained in the final scoring tool. The remaining 28 parameters were discarded: 4 had κ < 0.6 and were not deemed useful in predicting diagnosis; 9 were not visible on routinely acquired clinical images; and 15 had inter-rater agreement ≥0.6 but were not useful in differentiating monophasic ADEM, MS, and SV-cPACNS.CONCLUSIONS:We propose a 16-parameter MR imaging scoring tool that is straightforward to apply in the clinical setting and demonstrates high inter-rater agreement.
    American Journal of Neuroradiology 01/2013; · 3.17 Impact Factor
  • Robert T Naismith, Brenda L Banwell
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    ABSTRACT: Acute, noninfectious, inflammatory illnesses of the CNS encompass an increasingly diverse array of clinical and biological entities, including acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, and paraneoplastic and nonneoplastic antibody-associated encephalopathies. ADEM is classically a monophasic, inflammatory-mediated attack on the CNS, more frequently seen in children than adults.(1) According to international consensus criteria, ADEM in children is clinically defined by encephalopathy, polyfocal neurologic deficits, and typified by ill-defined multifocal lesions of the brain and potentially of the optic nerves and spinal cord.(2) In ADEM, a history of a prodromal illness in the days before the onset of neurologic deficits implicates microbial exposure as an inciting contribution to the subsequent host immune response. No single infectious agent has been causally linked to ADEM, however, and no reliable biomarker defines this illness. As such, ADEM may encompass either a spectrum of disorders or a spectrum of clinical phenotypes that share some common aspects of pathobiology. Refinements within the clinical continuum of acute inflammatory illnesses of the CNS are necessary when the existence of discernible subgroups compels the consideration of important implications for acute therapy and prognosis. In this issue of Neurology(®), Marchioni et al.(3) have made such a refinement by identifying a not uncommon subgroup of postinfectious ADEM in adults, which has mixed central and peripheral nervous system (PNS) involvement.
    Neurology 01/2013; · 8.25 Impact Factor
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    Brenda L Banwell
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    ABSTRACT: Recognition of multiple sclerosis (MS) and other acquired demyelinating disorders in children has increased significantly in the last decade. Consensus definitions that characterize the varied clinical presentations of acute demyelination, and proposed clinical and MRI criteria specific for MS in children have aided diagnostic consistency. Care of children with an acute demyelinating attack is influenced by clinical severity, with corticosteroids, immunoglobulin, and plasma exchange being the most commonly employed therapies. Children with confirmed MS are often managed with immunomodulatory therapies (interferon and glatiramer acetate) approved for the treatment of MS in adults. Routine assessment of hepatic and hematological cell indices are important to monitor for safety of interferon therapy. While clinical treatment trials of interferon and glatiramer acetate in pediatric MS have yet to be conducted, case series evidence supports clinical safety and relapse rate reduction in the pediatric MS population. Epidemiological studies have implicated place of residence during childhood as a key determinant of MS risk. As such, pediatric-onset MS provides an opportunity to explore these risk factors contemporaneous with the clinical onset of disease. Studies of vitamin D, microbial exposures, and parental smoking are areas under active investigation. Finally, research exploring primary immunological mechanisms and host responses in patients with pediatric-onset MS, who by virtue of their young age may harbor fewer extraneous immune abnormalities, may yield new insights into the fundamental pathobiology of MS.
    Handbook of Clinical Neurology 01/2013; 112:1263-74.
  • Leonard H Verhey, Brenda L Banwell
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    ABSTRACT: Acute nontraumatic myelopathies of childhood include inflammatory, infectious, and vascular etiologies. Inflammatory immune-mediated disorders of the spinal cord can be categorized as idiopathic isolated transverse myelitis, neuromyelitis optica, and multiple sclerosis. In recent years, human T-cell lymphotropic virus type 1, West Nile virus, enterovirus-71, and Lyme disease have been increasingly recognized as infectious etiologies of myelopathy, and poliomyelitis remains an important etiology in world regions where vaccination programs have not been universally available. Vascular etiologies include vasculopathies (systemic lupus erythematosus, small vessel primary angiitis of the central nervous system), arteriovenous malformations, and spinal cord infarction (fibrocartilaginous embolism, diffuse hypoxic ischemia-mediated infarction). Vascular myelopathies are less common than inflammatory and infectious myelopathies, but are more likely to lead to devastating clinical deficits. Current therapeutic strategies include acute anti-inflammatory treatment and rehabilitation. Stem cell transplantation, nerve graft implantation, and stimulation of endogenous repair mechanisms represent promising strategies for spinal cord repair.
    Handbook of Clinical Neurology 01/2013; 112:999-1017.

Publication Stats

3k Citations
686.75 Total Impact Points


  • 2013–2014
    • The Children's Hospital of Philadelphia
      • Department of Neurology
      Philadelphia, Pennsylvania, United States
    • Duke University Medical Center
      • Center for Human Genome Variation
      Durham, North Carolina, United States
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
  • 1999–2014
    • SickKids
      • Division of Neurology
      Toronto, Ontario, Canada
  • 2012
    • KK Women's and Children's Hospital
      • Department of Neurology Services
      Singapore, Singapore
  • 2011–2012
    • York University
      • Department of Psychology
      Toronto, Ontario, Canada
    • Université du Québec
      Québec, Quebec, Canada
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2005–2012
    • University of Toronto
      • • Division of Neurology
      • • Department of Nutritional Sciences
      • • Hospital for Sick Children
      Toronto, Ontario, Canada
  • 2008–2011
    • McGill University
      • McConnell Brain Imaging Centre
      Montréal, Quebec, Canada
    • McMaster University
      • Department of Pediatrics
      Hamilton, Ontario, Canada
  • 2010
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
  • 2009
    • University of Sydney
      • Discipline of Paediatrics and Child Health
      Sydney, New South Wales, Australia
  • 2004
    • Jaber Al Ahmad Al Jaber Al Sabah Hospital
      Al Kuwayt, Al Asimah Governorate, Kuwait
  • 2002
    • The University of Calgary
      • Department of Paediatrics
      Calgary, Alberta, Canada