Brenda Banwell

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

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Publications (212)1045.28 Total impact

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    ABSTRACT: Since its initial reports in the 19th century, neuromyelitis optica (NMO) had been thought to involve only the optic nerves and spinal cord. However, the discovery of highly specific anti-aquaporin-4 antibody diagnostic biomarker for NMO enabled recognition of more diverse clinical spectrum of manifestations. Brain MRI abnormalities in patients seropositive for anti-aquaporin-4 antibody are common and some may be relatively unique by virtue of localization and configuration. Some seropositive patients present with brain involvement during their first attack and/or continue to relapse in the same location without optic nerve and spinal cord involvement. Thus, characteristics of brain abnormalities in such patients have become of increased interest. In this regard, MRI has an increasingly important role in the differential diagnosis of NMO and its spectrum disorder (NMOSD), particularly from multiple sclerosis. Differentiating these conditions is of prime importance because early initiation of effective immunosuppressive therapy is the key to preventing attack-related disability in NMOSD, whereas some disease-modifying drugs for multiple sclerosis may exacerbate the disease. Therefore, identifying the MRI features suggestive of NMOSD has diagnostic and prognostic implications. We herein review the brain, optic nerve, and spinal cord MRI findings of NMOSD. © 2015 American Academy of Neurology.
    Full-text · Article · Feb 2015 · Neurology
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    ABSTRACT: Query of sun-related habits or ancestry could help screen for risk of vitamin D insufficiency (serum 25-hydroxyvitamin D<75nmol/L). We evaluated the association between Sun Exposure Score (calculated from recall of Time Exposed to Sun and Skin Exposed to Sun in the previous week), demographics and anthropometrics (including self-reported ancestry and skin melanin reflectometry), and serum 25(OH)D levels in healthy young Canadian adults in the Greater Toronto Area (GTA; 43°N) during fall. 310 adults (67% female) of European, East Asian, and South Asian ancestries were evaluated. The median (interquartile range) 25(OH)D level was 49.7nmol/L (36.7-70.3) and 80% of participants were vitamin D insufficient. The vast majority of those of East and South Asian ancestry were vitamin D insufficient (91% and 97%, respectively), as were 55% of those of European ancestry. Sun Exposure Score and 25(OH)D concentrations were not associated after accounting for confounders. A multivariable model showed ancestry, recent summer sun exposure, sex, melanin, vitamin D intake, age and year of study significantly predicted 25(OH)D concentration; ancestry was the strongest independent predictor (adjusted R(2)=43%). Although Sun Exposure Score was not a significant predictor of serum 25(OH)D levels, inquiry of ancestry has potential use in screening for vitamin D insufficiency. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Feb 2015 · Journal of Photochemistry and Photobiology B Biology
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    ABSTRACT: Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel aquaporin-4 present in up to 80% of NMO patients enables distinction from MS. Optic neuritis may occur in either condition resulting in neuro-anatomical retinal changes. Optical coherence tomography (OCT) has become a useful tool for analyzing retinal damage both in MS and NMO. Numerous studies showed that optic neuritis in NMO typically results in more severe retinal nerve fiber layer (RNFL) and ganglion cell layer thinning and more frequent development of microcystic macular edema than in MS. Furthermore, while patients' RNFL thinning also occurs in the absence of optic neuritis in MS, subclinical damage seems to be rare in NMO. Thus, OCT might be useful in differentiating NMO from MS and serve as an outcome parameter in clinical studies. © The Author(s), 2015.
    Full-text · Article · Feb 2015 · Multiple Sclerosis
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    ABSTRACT: Background: Cerebrospinal fluid opening pressure is elevated with central nervous system infection and vasculitis, but has not been studied in inflammatory demyelinating disease. This retrospective study sought to determine whether children with demyelinating disease demonstrate elevated cerebrospinal fluid opening pressure, and to explore possible clinical and radiologic correlates. Methods: Pediatric patients with acute disseminated encephalomyelitis, multiple sclerosis, or a clinically isolated syndrome (including optic neuritis and transverse myelitis) who had a lumbar puncture within 1 month of presentation were eligible for inclusion, and were compared with a reference cohort of healthy children from the same institution. Regression analyses were used to determine the association of variables collected with opening pressure. Results: Opening pressure was elevated in 15 of 53 (28%) children, which was significantly higher than the reference cohort (P = 0.001). There was no relationship between elevated opening pressure and any of the clinical or radiologic variables collected. Conclusion: Although almost one third of children with inflammatory demyelinating disease have an elevated cerebrospinal fluid opening pressure, the clinical and radiologic variables evaluated in this study did not explain this finding, and further understanding may require assessment of cerebrospinal fluid flow dynamics.
    No preview · Article · Jan 2015 · Pediatric Neurology
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    ABSTRACT: In multiple sclerosis (MS), cerebellar signs and symptoms as well as cognitive dysfunction are frequent and contribute to clinical disability with only poor response to symptomatic treatment. The current consensus paper highlights the broad range of clinical signs and symptoms of MS patients, which relate to cerebellar dysfunction. There is considerable evidence of cerebellar involvement in MS based on clinical, histopathological as well as structural and functional magnetic resonance imaging (MRI) studies. The review of the recent literature, however, also demonstrates a high variability of results. These discrepancies are, at least partially, caused by the use of different techniques and substantial heterogeneity among the patient cohorts in terms of disease duration, number of patients, and progressive vs. relapsing disease courses. Moreover, the majority of studies were crosssectional, providing little insight into the dynamics of cerebellar involvement in MS. Some links between the histopathological changes, the structural and functional abnormalities as captured by MRI, cerebellar dysfunction, and the clinical consequences are starting to emerge and warrant further study. A consensus is formed that this line of research will benefit from advances in neuroimaging techniques that allow to trace cerebellar involvement at higher resolution. Using a prospective study design, multimodal high-resolution cerebellar imaging is highly promising, particularly in patients who present with radiologically or clinically isolated syndromes or newly diagnosed MS.
    Full-text · Article · Jan 2015 · The Cerebellum
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    ABSTRACT: Children and adolescents diagnosed with multiple sclerosis rarely accrue physical disability early in their disease. This could be explained by greater remyelination in children, a capacity that may be lost in adolescence or early adulthood. Magnetization transfer ratio (MTR) MRI can be used to quantify changes in myelin in MS. We used serial MTR imaging and longitudinal random effects analysis to quantify recovery of MTR in acute lesions and to evaluate MTR changes in normal-appearing tissue in 19 adolescent MS patients. Our objective was to determine whether younger adolescents have a greater capacity for remyelination, and whether this decreases as patients approach adulthood. We detected a significant decrease in MTR recovery between ages 16 and 20 years (p = 0.023), with older subjects approaching typical recovery levels for adult-onset MS. MTR recovery in acute MS lesions decreases with age in adolescents, suggesting loss of remyelination capacity. This may be related to the conclusion of primary myelination, or other developmental factors.
    Full-text · Article · Dec 2014 · Clinical neuroimaging
  • Brenda Banwell · Russell C Dale
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    ABSTRACT: Acute transverse myelitis (TM) is a serious illness in both children and adults and can occur in the first year of life. Whereas severity at onset varies, many patients manifest with tetraplegia or paraplegia or marked loss of bowel and bladder control, and many require intensive care.
    No preview · Article · Dec 2014 · Neurology
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    ABSTRACT: For reasons that remain unclear, three times more women develop multiple sclerosis (MS) than men. This preponderance among women is evident only after 12 years of age, implicating pubertal factors in the risk of MS. To investigate the influence of female puberty on central nervous system (CNS) autoimmunity. We examined the relationship between age of menarche on MS outcomes in 116 female children (< 16 years old) whom presented with incident 'acquired demyelinating syndromes' (ADS) and were followed prospectively in the national Canadian Pediatric Demyelinating Disease Study, from 2004-2013. Furthermore, we directly investigated the effects of puberty on susceptibility to experimental autoimmune encephalomyelitis (EAE) in two groups of female mice that differed only in their pubertal status. In the ADS children, a later age of menarche was associated with a decreased risk of subsequent MS diagnosis. This relationship persisted, after accounting for patient age at ADS presentation and the presence of ≥1 T2 lesions on brain magnetic resonance imaging (MRI), with a hazard ratio (HR) of 0.64; and additional factors that associate with MS outcomes in ADS children, including low vitamin D levels. Furthermore, we found female mice that had transitioned through puberty were more susceptible to EAE than age-matched, pre-pubertal mice. Puberty in females enhances CNS autoimmune mechanisms that lead to MS in humans and EAE in mice. © The Author(s), 2014.
    No preview · Article · Dec 2014 · Multiple Sclerosis
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    ABSTRACT: Children and adolescents with relapsing-remitting multiple sclerosis (RRMS) have a similar T2 lesion burden as adults matched for disease duration. However, it is unknown whether the degree of tissue destruction within lesions is also similar. Persistent reduced T1-weighted signal intensity within lesions indicates loss of tissue integrity. We aimed to compare change over a 2-year period in T1 intensity within new T2 lesions, from pre-lesion levels to chronic post-lesion levels, between pediatric and adult-onset MS. A two-point intensity-normalization method was used to generate normalized T1-weighted (NT1) images from T1-weighted data in 29 pediatric MS patients (age(mean±SD, years), disease duration (years)=15.7±2.4, 3.9±2.6) and 24 adult MS patients (36.7±8.9, 6.9±4.8). Subjects were imaged at three consecutive timepoints, 1 year apart. For each subject, a 'new-T2' lesion mask was created and the NT1 intensities 'pre-lesion', 'peri-lesion' and 'post-lesion' were determined. A longitudinal model was used to capture NT1 changes. The NT1 in both groups failed to recover to pre-lesion values by 1 year post-lesion (p=0.0002), with children showing significantly better recovery than adults (p=0.0089). Both groups showed a significant chronic reduction of T1 intensity within new T2 lesions. However, children showed a significantly greater recovery of T1 intensity, suggesting that MS lesions in the pediatric MS population are less destructive, or that pediatric patients have greater reparative capacity. © The Author(s), 2014.
    No preview · Article · Dec 2014 · Multiple Sclerosis
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    Giulia Longoni · Brenda Banwell · Massimo Filippi · E Ann Yeh
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    ABSTRACT: No established therapeutic protocol has been proposed to date for childhood-onset neuromyelitis optica (NMO) spectrum disorders (NMOSDs). We report the response of 5 NMO immunoglobulin (Ig)G-positive pediatric cases to a standardized B-cell-targeted first-line immunosuppressive protocol with rituximab for prevention of relapses. Retrospective observational cohort study. All patients included in the study showed disease remission after rituximab induction. Relapses always occurred in conjunction with CD19(+) B-cell repopulation and appeared less severe than prior to treatment. At the end of follow-up, neurologic disability and MRI findings stabilized or improved in all the patients, with only minor and transient side effects. Oral steroid discontinuation was possible in all the patients. Our protocol is well-tolerated and has provided encouraging results in terms of control of relapses and progression of disability. An early intervention with rituximab might affect the disease course in pediatric NMO-IgG-positive NMOSDs. This study provides Class IV evidence that for children with NMOSDs, rituximab is well-tolerated and stabilizes or improves neurologic disability.
    Preview · Article · Dec 2014
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    ABSTRACT: Objectives: For most adults with initial clinical presentation of multiple sclerosis (MS), biological disease was likely initiated many years prior. Pediatric-onset MS provides an opportunity to study early disease processes. Methods: Using antigen microarrays, including CNS-related proteins, lipids, and other autoantigens, we studied early immunologic events involved in clinical onset of pediatric MS. Serum samples were collected at the time of incident acquired CNS demyelinating syndromes (ADS) in children who, in subsequent prospective follow-up, were ascertained to have either pediatric MS (ADS-MS) or a monophasic illness (ADS-mono). Samples were obtained both at the time of ADS presentation and 3 months into follow-up. We used an initial training set of samples to implicate antibody signatures associated with each group, and then a test set. An additional set of follow-up samples (stability set) was used as a form of internal validation. Results: Children with ADS-MS tended to have distinguishable serum antibody patterns both at the time of ADS presentation and 3 months into follow-up. At the time of ADS, serum samples from patients with ADS-MS or ADS-mono reacted against similar numbers of CNS antigens, although CNS antigens implicated in adult MS were more often targeted in children with ADS-MS. The follow-up ADS-MS samples reacted against a broader panel of CNS antigens, while corresponding ADS-mono samples exhibited a contraction of the initial antibody response. Conclusions: Our findings in this prospective cohort of pediatric-onset CNS demyelinating diseases point to an active process of epitope spreading during early stages of MS, not seen in monophasic CNS inflammatory conditions.
    Full-text · Article · Nov 2014 · Neurology
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    ABSTRACT: Objective: To determine the impact of pediatric-onset multiple sclerosis (MS) on age-expected brain growth. Methods: Whole brain and regional volumes of 36 patients with relapsing-remitting MS onset prior to 18 years of age were segmented in 185 longitudinal MRI scans (2-11 scans per participant, 3-month to 2-year scan intervals). MRI scans of 25 age- and sex-matched healthy normal controls (NC) were also acquired at baseline and 2 years later on the same scanner as the MS group. A total of 874 scans from 339 participants from the NIH-funded MRI study of normal brain development acquired at 2-year intervals were used as an age-expected healthy growth reference. All data were analyzed with an automatic image processing pipeline to estimate the volume of brain and brain substructures. Mixed-effect models were built using age, sex, and group as fixed effects. Results: Significant group and age interactions were found with the adjusted models fitting brain volumes and normalized thalamus volumes (p < 10(-4)). These findings indicate a failure of age-normative brain growth for the MS group, and an even greater failure of thalamic growth. In patients with MS, T2 lesion volume correlated with a greater reduction in age-expected thalamic volume. To exclude any scanner-related influence on our data, we confirmed no significant interaction of group in the adjusted models between the NC and NIH MRI Study of Normal Brain Development groups. Conclusions: Our results provide evidence that the onset of MS during childhood and adolescence limits age-expected primary brain growth and leads to subsequent brain atrophy, implicating an early onset of the neurodegenerative aspect of MS.
    No preview · Article · Nov 2014 · Neurology
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    ABSTRACT: Objective: We evaluated the relationship of optical coherence tomography (OCT)-measured ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL) thickness to other functional measures of afferent visual pathway competence including high-contrast visual acuity (HCVA) and low-contrast visual acuity (LCVA), visual field sensitivity, and color vision perception in a pediatric population with demyelinating disorders. Methods: This was a cross-sectional evaluation of 37 children, aged 8-18 years, with pediatric demyelinating disorders (n = 74 eyes), and 18 healthy controls (n = 36 eyes), who were recruited from the University of Toronto, Hospital for Sick Children and the University of Calgary, Alberta Children's Hospital, Canada. A standardized visual battery, including spectral-domain OCT, visual fields, LCVA, and HCVA, was performed in all subjects. Results: Mean RNFL thickness was 26 µm (25.6%) lower in patients with demyelination (76.2 μm [3.7]) compared to controls (102.4 μm [2.1]) (p < 0.0001). Mean GCL thickness was 20% lower in patients as compared to controls (p < 0.0001). Mean GCL and RNFL thickness were strongly correlated (r = 0.89; p < 0.0001), yet in contrast to RNFL thickness, no differences in GCL thickness were noted between optic neuritis (ON) eyes and non-ON eyes of patients. HCVA and LCVA and visual field mean deviation scores decreased linearly with lower RNFL thickness. Conclusion: GCL thickness was decreased in patients regardless of history of ON. The retina may be a site of primary neuronal injury in pediatric demyelination.
    Preview · Article · Oct 2014 · Neurology

  • No preview · Article · Oct 2014 · Journal of Neuroimmunology

  • No preview · Article · Oct 2014 · Journal of Neuroimmunology
  • Sandra Bigi · Brenda Banwell · E Ann Yeh
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    ABSTRACT: The use of plasma exchange has been described in steroid-refractory central nervous system inflammatory demyelination in adults, but less has been published regarding its use in children and adolescents. We describe 12 children treated with plasma exchange for acute severe central nervous system inflammatory demyelination. The clinical attack leading to plasma exchange included symptomatic spinal cord lesions in 10 and symptomatic brainstem lesions in 2 children. Diagnosis was acute transverse myelitis in 6, relapsing-remitting multiple sclerosis in 5, and acute disseminated encephalomyelitis in 1 child. Adverse events related to plasma exchange necessitating intervention were observed in 3 children. Median Expanded Disability Status Scale score at plasma exchange start was 7.5 (range 4-9.5). At 3 months, 7 children were ambulatory without aid (Expanded Disability Status Scale score of ≤4). This retrospective study suggests that plasma exchange can be effective in ameliorating symptoms in severe pediatric central nervous system inflammatory demyelination, although lack of randomization or control group limits the ability to attribute this outcome entirely to plasma exchange.
    No preview · Article · Sep 2014 · Journal of Child Neurology
  • S. Bigi · R. Marrie · C. Till · N. Akbar · E. Yeh · A. Feinstein · B. Banwell

    No preview · Article · Sep 2014 · Neuropediatrics

  • No preview · Article · Sep 2014 · Neuropediatrics
  • Brenda Banwell · Gavin Giovannoni · Chris Hawkes · Fred Lublin

    No preview · Article · Sep 2014 · Multiple Sclerosis and Related Disorders
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    ABSTRACT: The clinical features, diagnostic challenges, neuroimaging appearance, therapeutic options, and pathobiological research progress in childhood—and adolescent—onset multiple sclerosis have been informed by many new insights in the past 7 years. National programmes in several countries, collaborative research efforts, and an established international paediatric multiple sclerosis study group have contributed to revised clinical diagnostic definitions, identified clinical features of multiple sclerosis that differ by age of onset, and made recommendations regarding the treatment of paediatric multiple sclerosis. The relative risks conveyed by genetic and environmental factors to paediatric multiple sclerosis have been the subject of several large cohort studies. MRI features have been characterised in terms of qualitative descriptions of lesion distribution and applicability of MRI aspects to multiple sclerosis diagnostic criteria, and quantitative studies have assessed total lesion burden and the effect of the disease on global and regional brain volume. Humoral-based and cell-based assays have identified antibodies against myelin, potassium-channel proteins, and T-cell profiles that support an adult-like T-cell repertoire and cellular reactivity against myelin in paediatric patients with multiple sclerosis. Finally, the safety and efficacy of standard first-line therapies in paediatric multiple sclerosis populations are now appreciated in more detail, and consensus views on the future conduct and feasibility of phase 3 trials for new drugs have been proposed.
    No preview · Article · Sep 2014 · The Lancet Neurology

Publication Stats

7k Citations
1,045.28 Total Impact Points

Institutions

  • 2013-2016
    • The Children's Hospital of Philadelphia
      • • Department of Neurology
      • • Department of Pediatrics
      Filadelfia, Pennsylvania, United States
    • Icahn School of Medicine at Mount Sinai
      • Department of Neurology
      Borough of Manhattan, New York, United States
  • 2013-2015
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 2001-2015
    • University of Toronto
      • • Department of Paediatrics
      • • Hospital for Sick Children
      • • Division of Neurology
      Toronto, Ontario, Canada
  • 2001-2014
    • SickKids
      • Division of Neurology
      Toronto, Ontario, Canada
  • 2008
    • University of British Columbia - Vancouver
      • Department of Radiology
      Vancouver, British Columbia, Canada
  • 1999
    • University of Michigan
      Ann Arbor, Michigan, United States