Brenda Banwell

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

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Publications (186)960.12 Total impact

  • Neuropediatrics 09/2014; 45(S 01). DOI:10.1055/s-0034-1390561 · 1.10 Impact Factor
  • Neuropediatrics 09/2014; 45(S 01). DOI:10.1055/s-0034-1390598 · 1.10 Impact Factor
  • 09/2014; 3(5):553–554. DOI:10.1016/j.msard.2014.02.002
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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 · 21.82 Impact Factor
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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 · 2.79 Impact Factor
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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; DOI:10.1017/S1355617714000642 · 3.01 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 · 8.30 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 · 1.82 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; DOI:10.1212/WNL.0000000000000560 · 8.30 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 · 5.30 Impact Factor
  • International Society for Magnetic Resonance in Medicine (ISMRM), Milan, Italy; 05/2014
  • Joint Congress of European Neurology; 05/2014
  • 03/2014; 3(2):139–140. DOI:10.1016/j.msard.2013.12.006
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    ABSTRACT: We report on a girl with a de novo mosaic derivative chromosome 17 involving a 7.4 Mb deletion of chromosome region 17p11.2 to 17p12 and a duplication of a 12.35 Mb region at 17q22 to 17q24. She was ascertained because of developmental delay, peripheral neuropathy, brachydactyly and minor anomalies. The derivative chromosome was present in approximately 12% of lymphocytes based on FISH studies, and was detected by array comparative genomic hybridization. To our knowledge, this is the third case of mosaicism involving deletion of the 17p11.2 region and the lowest level of mosaicism reported in a patient with Smith-Magenis syndrome (SMS). © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 03/2014; 164(3). DOI:10.1002/ajmg.a.36322 · 2.05 Impact Factor
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    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 cm3: 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.
    PLoS ONE 02/2014; 9(2):1-6. DOI:10.1371/journal.pone.0085741 · 3.53 Impact Factor
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    ABSTRACT: Impairments in visuospatial abilities are commonly reported in children and adolescents with multiple sclerosis (MS). Corpus callosum (CC) pathology occurs in patients with MS and may contribute to impairment in visuospatial perception, particularly when interhemispheric information transfer is required. This study used a global-local hierarchical letter paradigm to examine the relationship between interhemispheric information transfer and white matter integrity in the CC assessed using diffusion tensor imaging. Thirteen cognitively preserved pediatric-onset MS patients and 15 age-matched healthy controls were asked to determine whether a target letter E appeared at the attended level of the stimulus. As expected, both groups processed global and local information more slowly under divided than selective attention conditions. The MS group performed similarly to the control group with respect to reaction time and accuracy on selective and divided attention conditions, with one exception. Specifically, the presence of a global target when attending to a local target caused greater response conflict in the MS group than in controls (p = .01). Pooling both the patient and control data, greater response conflict was associated with reduced white matter integrity as indicated by lower fractional anisotropy in the anterior body of the CC (r = -.33, p < .05). Results suggest that reduced white matter integrity in anterior regions of the CC may lead to less efficient inhibition of task-irrelevant global information in the hierarchal processing of visual information.
    Journal of Clinical and Experimental Neuropsychology 01/2014; DOI:10.1080/13803395.2013.867013 · 2.16 Impact Factor
  • S Bigi, Ra Marrie, Ea Yeh, B Banwell
    Multiple Sclerosis 01/2014; 20(12). DOI:10.1177/1352458513518263 · 4.86 Impact Factor
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    ABSTRACT: To investigate whether 57 genetic risk loci recently identified in a large-scale genome-wide association study in adult patients with multiple sclerosis (MS) are also associated with a risk for pediatric-onset MS and whether they can predict MS diagnosis in children presenting with acquired demyelinating syndromes (ADS). We included 188 children with ADS, of whom 53 were diagnosed with MS, 466 patients with adult-onset MS, and 2,046 adult controls in our cohort study. Weighted genetic risk scores (wGRS) were calculated to evaluate genetic effects. Mean wGRS was significantly higher for patients with pediatric-onset MS (7.32 ± 0.53) as compared with patients with monophasic ADS (7.10 ± 0.47, p = 0.01) and controls (7.11 ± 0.53, p < 0.01). We found no difference in mean wGRS of participants with monophasic ADS (7.10 ± 0.47) and controls (7.11 ± 0.53). The ability of the wGRS for the 57 single nucleotide polymorphisms (SNPs) to discriminate between children with MS and those with monophasic ADS was moderate (area under the curve [AUC] = 0.64), but improved with the addition of sex and HLA-DRB1*15 (AUC = 0.70). The combined effect of 57 SNPs exceeded the effect of HLA-DRB1*15 alone in our risk models for pediatric- and adult-onset MS. The previously reported 57 SNPs for adult-onset MS also confer increased susceptibility to pediatric-onset MS, but not to monophasic ADS.
    Neurology 11/2013; 81(23). DOI:10.1212/01.wnl.0000436934.40034eb · 8.30 Impact Factor
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    Dataset: mmc1
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Publication Stats

5k Citations
960.12 Total Impact Points


  • 2013–2015
    • The Children's Hospital of Philadelphia
      • • Department of Neurology
      • • Department of Pediatrics
      Filadelfia, Pennsylvania, United States
    • McMaster University
      Hamilton, Ontario, Canada
    • Icahn School of Medicine at Mount Sinai
      Borough of Manhattan, New York, United States
  • 2013–2014
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 2002–2014
    • University of Toronto
      • • Department of Paediatrics
      • • Hospital for Sick Children
      • • Division of Neurology
      Toronto, Ontario, Canada
  • 1999–2014
    • SickKids
      • Division of Neurology
      Toronto, Ontario, Canada
  • 2011–2012
    • York University
      • Department of Psychology
      Toronto, Ontario, Canada
  • 2010
    • Sir Charles Gairdner Hospital
      Perth City, Western Australia, Australia
  • 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
  • 1999–2000
    • Mayo Clinic - Rochester
      • Department of Neurology
      Рочестер, Minnesota, United States