Brenda Banwell

William Penn University, Filadelfia, Pennsylvania, United States

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Publications (200)1020.92 Total impact

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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.
    Multiple Sclerosis 12/2014; 21(6). DOI:10.1177/1352458514551594 · 4.82 Impact Factor
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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.
    12/2014; 1(4):e46. DOI:10.1212/NXI.0000000000000046
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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.
    Neurology 11/2014; 83(24). DOI:10.1212/WNL.0000000000001066 · 8.29 Impact Factor
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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.
    Neurology 11/2014; 83(23). DOI:10.1212/WNL.0000000000001045 · 8.29 Impact Factor
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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.
    Neurology 10/2014; 83(23). DOI:10.1212/WNL.0000000000001046 · 8.29 Impact Factor

  • Journal of Neuroimmunology 10/2014; 275(1-2):90-91. DOI:10.1016/j.jneuroim.2014.08.242 · 2.47 Impact Factor

  • Journal of Neuroimmunology 10/2014; 275(1-2):203-204. DOI:10.1016/j.jneuroim.2014.08.547 · 2.47 Impact Factor
  • 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.
    Journal of Child Neurology 09/2014; 30(7). DOI:10.1177/0883073814545883 · 1.72 Impact Factor
  • S. Bigi · R. Marrie · C. Till · N. Akbar · E. Yeh · A. Feinstein · B. Banwell ·

    Neuropediatrics 09/2014; 45(S 01). DOI:10.1055/s-0034-1390561 · 1.24 Impact Factor

  • Neuropediatrics 09/2014; 45(S 01). DOI:10.1055/s-0034-1390598 · 1.24 Impact Factor
  • Brenda Banwell · Gavin Giovannoni · Chris Hawkes · Fred Lublin ·

    Multiple Sclerosis and Related Disorders 09/2014; 3(5):553–554. DOI:10.1016/j.msard.2014.02.002 · 0.88 Impact Factor
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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.
    The Lancet Neurology 09/2014; 13(9):936–948. DOI:10.1016/S1474-4422(14)70093-6 · 21.90 Impact Factor
  • Robert Thompson Stone · Brenda Banwell ·
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    ABSTRACT: The onset of multiple sclerosis (MS) occurs during childhood or adolescence in 3–10% of all patients. This chapter emphasizes the clinical, neuroimaging, epidemiologic, and treatment aspects of pediatric-onset MS and summarizes current means to distinguish MS from other forms of acquired demyelinating disease.
    Multiple Sclerosis and CNS Inflammatory Disorders, 08/2014: pages 77-90; , ISBN: 9780470673881
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    ABSTRACT: Altered cerebrovascular blood flow has been proposed as a mechanism for multiple sclerosis (MS). The primary objective of this study was to measure arterial and venous blood flow in adolescent MS patients and healthy controls (HC), in whom confounding factors such as age and lifestyle are less influential. Phase-contrast magnetic resonance imaging (MRI) was used to measure flow in 26 MS patients and 26 controls aged 17.7 ± 1.8 and 17.8 ± 2.1 years, respectively. Flow was measured in the left and right internal carotid arteries (ICA), vertebral arteries (VA), internal jugular veins (IJV), and epidural veins (EV). Eighteen MS patients returned for a second MRI examination after 6 months. In all participants, ultrasound criteria for chronic cerebrospinal venous insufficiency (CCSVI) were also evaluated. Flows (mL/min) in the MS group versus HC group were as follows: right ICA = 262 ± 57 vs. 263 ± 32, left ICA = 260 ± 67 vs. 270 ± 36, right VA = 96 ± 50 vs. 103 ± 30, left VA = 104 ± 37 vs. 118 ± 41, right IJV = 342 ± 180 vs. 345 ± 195, left IJV = 190 ± 131 vs. 250 ± 148, right EV = 33 ± 29 vs. 48 ± 43, and left EV = 36 ± 35 vs. 44 ± 28 (P > 0.17 for all comparisons). In MS participants, a nonsignificant trend to lower flow in the left IJV was observed, and the flow pulsatility index in the epidural veins was higher. Two MS participants met ultrasound criteria for CCSVI, but no significant difference in flow was detected. No population difference in flow rate was detected in adolescent MS participants relative to age-matched controls. J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 08/2014; 40(2). DOI:10.1002/jmri.24388 · 3.21 Impact Factor
  • Banafsheh Hosseini · David B Flora · Brenda L Banwell · Christine Till ·
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    ABSTRACT: Cognitive impairment is often reported in pediatric-onset multiple sclerosis (MS). Using serial cognitive data from 35 individuals with pediatric-onset MS, this study examined how age at disease-onset and proxies of cognitive reserve may impact cognitive maturation over the course of childhood and adolescence. Neuropsychological evaluations were conducted at baseline and up to four more assessments. Of the 35 participants, 7 completed only one assessment, 5 completed two assessments, 13 completed three assessments, 10 completed four or more assessments. Growth curve modeling was used to assess longitudinal trajectories on the Trail Making Test-Part B (TMT-B) and the Symbol Digit Modalities (SDMT; oral version) and to examine how age at disease onset, baseline Full Scale IQ, and social status may moderate rate of change on these measures. Mean number of evaluations completed per patient was 2.8. Younger age at disease onset was associated with a greater likelihood of cognitive decline on both the TMT-B (p=.001) and SDMT (p=.005). Baseline IQ and parental social status did not moderate any of the cognitive trajectories. Findings suggest that younger age at disease-onset increases the vulnerability for disrupted performance on measures of information processing, visual scanning, perceptual/motor speed, and working memory. Proxies of cognitive reserve did not protect against the progression of decline on these measures. Young patients with MS should be advised to seek follow-up cognitive evaluation to assess cognitive maturation and to screen for the potential late emergence of cognitive deficits. (JINS, 2014, 20, 1-9).
    Journal of the International Neuropsychological Society 07/2014; 20(08):1-9. DOI:10.1017/S1355617714000642 · 2.96 Impact Factor
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    ABSTRACT: Abstract Objective: To assess the utility and safety of rituximab in paediatric autoimmune and inflammatory disorders of the CNS. Methods: Multicentre retrospective study. Results: 144 children and adolescents (median age 8 years, range 0.7-17; 103 females) with NMDAR encephalitis (n=39), opsoclonus myoclonus ataxia syndrome (n=32), neuromyelitis optica spectrum disorders (n=20), neuropsychiatric systemic lupus erythematosus (n=18), and other neuro-inflammatory disorders (n=35) were studied at onset of neurological disease. Rituximab was given after a median duration of disease of 0.5 years (range 0.05-9.5 years). Infusion adverse events were recorded in 18/144 (12.5%) including Grade 4 (anaphylaxis) in three. 11 patients (7.6%) had an infectious adverse event (AE), including two with Grade 5 (death) and two with Grade 4 (disabling) infectious AE (median follow-up of 1.65 years (range 0.1-8.5). No patients developed progressive multifocal leukoencephalopathy. A definite, probable or possible benefit was reported in 125 of 144 (87%) patients. 17.4% of patients had a modified Rankin scale (mRS) of 0-2 at rituximab initiation, compared to 73.9% at outcome. The change in mRS 0-2 was greater in patients given rituximab early in their disease course compared to those treated later. Conclusion: While limited by the retrospective nature of this analysis, our data supports an off-label use of rituximab, although the significant risk of infectious complications suggests rituximab should be restricted to disorders with significant morbidity and mortality. Classification of Evidence: This study provides Class IV evidence that in paediatric autoimmune and inflammatory CNS disorders, rituximab improves neurologic outcomes with a 7.6% risk of adverse infections.
    Neurology 07/2014; 83(2). DOI:10.1212/WNL.0000000000000570 · 8.29 Impact Factor
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    ABSTRACT: BACKGROUND Intensity variation between magnetic resonance images (MRI) hinders comparison of tissue intensity distributions in multicenter MRI studies of brain diseases. The available intensity normalization techniques generally work well in healthy subjects but not in the presence of pathologies that affect tissue intensity. One such disease is multiple sclerosis (MS), which is associated with lesions that prominently affect white matter (WM). OBJECTIVE To develop a T1-weighted (T1w) image intensity normalization method that is independent of WM intensity, and to quantitatively evaluate its performance. METHODS AND SUBJECTSWe calculated median intensity of grey matter and intraconal orbital fat on T1w images. Using these two reference tissue intensities we calculated a linear normalization function and applied this to the T1w images to produce normalized T1w (NT1) images. We assessed performance of our normalization method for interscanner, interprotocol, and longitudinal normalization variability, and calculated the utility of the normalization method for lesion analyses in clinical trials. RESULTSStatistical modeling showed marked decreases in T1w intensity differences after normalization (P < .0001). CONCLUSIONS We developed a WM-independent T1w MRI normalization method and tested its performance. This method is suitable for longitudinal multicenter clinical studies for the assessment of the recovery or progression of disease affecting WM.
    Journal of neuroimaging: official journal of the American Society of Neuroimaging 06/2014; 25(2). DOI:10.1111/jon.12129 · 1.73 Impact Factor
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    ABSTRACT: Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined. Open access full paper at //
    Neurology 05/2014; 83(3). DOI:10.1212/WNL.0000000000000560 · 8.29 Impact Factor
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    ABSTRACT: Primary human herpesvirus 7 (HHV-7) infection occurs almost universally during the first 5 years of life and is rarely accompanied by central nervous system (CNS) symptoms such as febrile seizures. The present retrospective study investigated the role of primary HHV-7 infection in CNS disease in children, including adolescents. The study included all children who had neurologic disease aged younger than 18 years seen at the Hospital for Sick Children, Toronto, Canada, between April 1, 1998 and December 31, 2011, whose cerebrospinal fluid (CSF) was found by polymerase chain reaction to contain HHV-7 DNA. Where sera were available, HHV-7 IgG antibody titers and avidity were measured to differentiate primary from past infection. HHV-7 DNA was detected in the CSF of 57 (1.9%) of the 2972 children tested. In 3 adolescents primary HHV-7 infection (low avidity IgG) was confirmed as the cause of neurologic disease, 2 who had encephalitis and 1 who had Guillain-Barré syndrome. Eighteen children had possible HHV-7 disease (no alternative cause identified and indeterminate antibody result or serum not available), 7 encephalitis, 8 meningitis, and 3 demyelinating disorders. HHV-7 disease was excluded in 36 children on the basis of past infection (high IgG avidity) and/or an alternative cause. Primary HHV-7 infection delayed into adolescence can cause serious neurologic disease. HHV-7 DNA in CSF alone is insufficient to prove an etiologic association. Combining CSF polymerase chain reaction with serology is essential to prove primary infection when investigating HHV-7 CNS disease.
    PEDIATRICS 05/2014; 133(6). DOI:10.1542/peds.2013-3344 · 5.47 Impact Factor

  • International Society for Magnetic Resonance in Medicine (ISMRM), Milan, Italy; 05/2014

Publication Stats

6k Citations
1,020.92 Total Impact Points


  • 2013-2015
    • William Penn University
      Filadelfia, Pennsylvania, United States
    • 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
  • 2002-2015
    • University of Toronto
      • • Department of Paediatrics
      • • Hospital for Sick Children
      • • Division of Neurology
      Toronto, Ontario, Canada
  • 2003-2014
    • SickKids
      • Division of Neurology
      Toronto, Ontario, Canada
  • 2011
    • York University
      • Department of Psychology
      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