Person:
Glanz, Bonnie

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Glanz

First Name

Bonnie

Name

Glanz, Bonnie

Filters

2010 - 201717

Settings

Author's Publications: search.filters.isAuthorOfPublication.fd59756e-a0a4-43be-9d6a-bfadd70b5443

Search Results

Now showing 1 - 10 of 17
  • Thumbnail Image
    Publication
    Microstructural Changes in the Striatum and Their Impact on Motor and Neuropsychological Performance in Patients with Multiple Sclerosis
    (Public Library of Science, 2014) Cavallari, Michele; Ceccarelli, Antonia; Wang, Guang-Yi; Moscufo, Nicola; Hannoun, Salem; Matulis, Christina R.; Jackson, Jonathan S.; Glanz, Bonnie; Bakshi, Rohit; Neema, M; Guttmann, Charles
    Grey matter (GM) damage is a clinically relevant feature of multiple sclerosis (MS) that has been previously assessed with diffusion tensor imaging (DTI). Fractional anisotropy (FA) of the basal ganglia and thalamus might be increased in MS patients, and correlates with disability scores. Despite the established role of the striatum and thalamus in motor control, mood and cognition, the impact of DTI changes within these structures on motor and neuropsychological performance has not yet been specifically addressed in MS. We investigated DTI metrics of deep GM nuclei and their potential association with mobility and neuropsychological function. DTI metrics from 3T MRI were assessed in the caudate, putamen, and thalamus of 30 MS patients and 10 controls. Sixteen of the patients underwent neuropsychological testing. FA of the caudate and putamen was higher in MS patients compared to controls. Caudate FA correlated with Expanded Disability Status Scale score, Ambulation Index, and severity of depressive symptomatology. Putamen and thalamus FA correlated with deficits in memory tests. In contrast, cerebral white matter (WM) lesion burden showed no significant correlation with any of the disability, mobility and psychometric parameters. Our findings support evidence of FA changes in the basal ganglia in MS patients, as well as deep GM involvement in disabling features of MS, including mobility and cognitive impairment. Deep GM FA appears to be a more sensitive correlate of disability than WM lesion burden.
  • Thumbnail Image
    Publication
    An expanded composite scale of MRI-defined disease severity in multiple sclerosis: MRDSS2
    (Lippincott Williams & Wilkins, 2014) Bakshi, Rohit; Neema, M; Tauhid, Shahamat; Healy, Brian C.; Glanz, Bonnie; Kim, Gloria; Miller, Jennifer; Berkowitz, Julia L.; Bove, Riley; Houtchens, Maria; Severson, Christopher; Stankiewicz, James; Stazzone, Lynn; Chitnis, Tanuja; Guttmann, Charles R.G.; Weiner, Howard; Ceccarelli, Antonia
    The objective of this study was to test a new version of the Magnetic Resonance Disease Severity Scale (MRDSS2), incorporating cerebral gray matter (GM) and spinal cord involvement from 3 T MRI, in modeling the relationship between MRI and physical disability or cognitive status in multiple sclerosis (MS). Fifty-five MS patients and 30 normal controls underwent high-resolution 3 T MRI. The patients had an Expanded Disability Status Scale score of 1.6±1.7 (mean±SD). The cerebral normalized GM fraction (GMF), the T2 lesion volume (T2LV), and the ratio of T1 hypointense LV to T2LV (T1/T2) were derived from brain images. Upper cervical spinal cord area (UCCA) was obtained from spinal cord images. A within-subject d-score (difference of MS from normal control) for each MRI component was calculated, equally weighted, and summed to form MRDSS2. With regard to the relationship between physical disability and MRDSS2 or its individual components, MRI–Expanded Disability Status Scale correlations were significant for MRDSS2 (r=0.33, P=0.013) and UCCA (r=−0.33, P=0.015), but not for GMF (P=0.198), T2LV (P=0.707), and T1/T2 (P=0.240). The inclusion of UCCA appeared to drive this MRI–disability relationship in MRDSS2. With regard to cognition, MRDSS2 showed a larger effect size (P=0.035) than its individual components [GMF (P=0.081), T2LV (P=0. 179), T1/T2 (P=0.043), and UCCA (P=0.818)] in comparing cognitively impaired with cognitively preserved patients (defined by the Minimal Assessment of Cognitive Function in MS). Both cerebral lesions (T1/T2) and atrophy (GMF) appeared to drive this relationship. We describe a new version of the MRDSS, which has been expanded to include cerebral GM and spinal cord involvement. MRDSS2 has concurrent validity with clinical status.
  • Thumbnail Image
    Publication
    Alterations of the human gut microbiome in multiple sclerosis
    (Nature Publishing Group, 2016) Jangi, Sushrut; Gandhi, Roopali; Cox, Laura; Li, Ning; von Glehn, Felipe; Yan, Raymond; Patel, Bonny; Mazzola, Maria; Liu, Shirong; Glanz, Bonnie; Cook, Sandra; Tankou, Stephanie; Stuart, Fiona; Melo, Kirsy; Nejad, Parham; Smith, Kathleen; Topçuolu, Begüm D.; Holden, James; Kivisakk, Pia; Chitnis, Tanuja; De Jager, Philip; Quintana, Francisco; Gerber, Georg; Bry, Lynn; Weiner, Howard
    The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Here we use 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n=60) and healthy controls (n=43). Microbiome alterations in MS include increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella, and decreased Sarcina, compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis.
  • Thumbnail Image
    Publication
    Identification of a novel mechanism of action of fingolimod (FTY720) on human effector T cell function through TCF-1 upregulation
    (BioMed Central, 2015) Mazzola, Maria; Raheja, Radhika; Murugaiyan, Gopal; Rajabi, Hasan; Kumar, Deepak; Pertel, Thomas; Regev, Keren; Griffin, Russell; Aly, Lilian; Kivisakk, Pia; Nejad, Parham; Patel, Bonny; Gwanyalla, Nguendab; Hei, Hillary; Glanz, Bonnie; Chitnis, Tanuja; Weiner, Howard; Gandhi, Roopali
    Background: Fingolimod (FTY720), the first oral treatment for multiple sclerosis (MS), blocks immune cell trafficking and prevents disease relapses by downregulation of sphingosine-1-phosphate receptor. We determined the effect of FTY720 on human T cell activation and effector function. Methods: T cells from MS patients and healthy controls were isolated to measure gene expression profiles in the presence or absence of FTY720 using nanostring and quantitative real-time polymerase chain reaction (qPCR). Cytokine protein expression was measured using luminex assay and flow cytometry analysis. Lentivirus vector carrying short hairpin RNA (shRNA) was used to knock down the expression of specific genes in CD4+ T cells. Chromatin immunoprecipitation was performed to assess T cell factor 1 (TCF-1) binding to promoter regions. Luciferase assays were performed to test the direct regulation of interferon gamma (IFN-γ) and granzyme B (GZMB) by TCF-1. Western blot analysis was used to assess the phosphorylation status of Akt and GSK3β. Results: We showed that FTY720 treatment not only affects T cell trafficking but also T cell activation. Patients treated with FTY720 showed a significant reduction in circulating CD4 T cells. Activation of T cells in presence of FTY720 showed a less inflammatory phenotype with reduced production of IFN-γ and GZMB. This decreased effector phenotype of FTY720-treated T cells was dependent on the upregulation of TCF-1. FTY720-induced TCF-1 downregulated the pathogenic cytokines IFN-γ and GZMB by binding to their promoter/enhancer regions and mediating epigenetic modifications. Furthermore, we observed that TCF-1 expression was lower in T cells from multiple sclerosis patients than in those from healthy individuals, and FTY720 treatment increased TCF-1 expression in multiple sclerosis patients. Conclusions: These results reveal a previously unknown mechanism of the effect of FTY720 on human CD4+ T cell modulation in multiple sclerosis and demonstrate the role of TCF-1 in human T cell activation and effector function. Electronic supplementary material The online version of this article (doi:10.1186/s12974-015-0460-z) contains supplementary material, which is available to authorized users.
  • No Thumbnail Available
    Publication
    Quantitative MRI study of Pineal Gland in MS.
    (2016) Egorova, Svetlana; Denes, Palma; Polgar-Turcsanyi, Mariann; Anderson, Mark; Cavallari, Michele; Guttmann, Charles; Glanz, Bonnie; Chitnis, Tanuja; Bove, Riley; Buckle, Guy; De Jager, Philip; Severson, Cristopher; Stankiewicz, James; Houtchens, Maria; Quintana, Francisco; Gandhi, Roopali; Webb, Pia; Meier, Dominik; Healy, Brian; Weiner, Howard
  • Thumbnail Image
    Publication
    Comprehensive evaluation of serum microRNAs as biomarkers in multiple sclerosis
    (Lippincott Williams & Wilkins, 2016) Regev, Keren; Paul, Anu; Healy, Brian; von Glenn, Felipe; Diaz-Cruz, Camilo; Gholipour, Taha; Mazzola, Maria; Raheja, Radhika; Nejad, Parham; Glanz, Bonnie; Kivisakk, Pia; Chitnis, Tanuja; Weiner, Howard; Gandhi, Roopali
    Objective: To identify circulating microRNAs (miRNAs) linked to disease stage and disability in multiple sclerosis (MS). Methods: Sera from 296 participants including patients with MS, other neurologic diseases (Alzheimer disease and amyotrophic lateral sclerosis), and inflammatory diseases (rheumatoid arthritis and asthma) and healthy controls (HCs) were tested. miRNA profiles were determined using LNA (locked nucleic acid)-based quantitative PCR. Patients with MS were categorized according to disease stage and disability. In the discovery phase, 652 miRNAs were measured in sera from 26 patients with MS and 20 HCs. Following this, significant miRNAs (p < 0.05) from the discovery set were validated using quantitative PCR in 58 patients with MS, 30 HCs, and in 74 samples from other disease controls (Alzheimer disease, amyotrophic lateral sclerosis, asthma, and rheumatoid arthritis). Results: We validated 7 miRNAs that differentiate patients with MS from HCs (p < 0.05 in both the discovery and validation phase); miR-320a upregulation was the most significantly changing serum miRNA in patients with MS. We also identified 2 miRNAs linked to disease progression, with miR-27a-3p being the most significant. Ten miRNAs correlated with the Expanded Disability Status Scale of which miR.199a.5p had the strongest correlation with disability. Of the 15 unique miRNAs we identified in the different group comparisons, 12 have previously been reported to be associated with MS but not in serum. Conclusions: Our findings identify circulating serum miRNAs as potential biomarkers to diagnose and monitor disease status in MS. Classification of evidence: This study provides Class III evidence that circulating serum miRNAs can be used as biomarker for MS.
  • Thumbnail Image
    Publication
    Evaluating more naturalistic outcome measures: A 1-year smartphone study in multiple sclerosis
    (Lippincott Williams & Wilkins, 2015) Bove, Riley; White, Charles C.; Giovannoni, Gavin; Glanz, Bonnie; Golubchikov, Victor; Hujol, Johnny; Jennings, Charles; Langdon, Dawn; Lee, Michelle; Legedza, Anna; Paskavitz, James; Prasad, Sashank; Richert, John; Robbins, Allison; Roberts, Susan; Weiner, Howard; Ramachandran, Ravi; Botfield, Martyn; De Jager, Philip
    Objective: In this cohort of individuals with and without multiple sclerosis (MS), we illustrate some of the novel approaches that smartphones provide to monitor patients with chronic neurologic disorders in their natural setting. Methods: Thirty-eight participant pairs (MS and cohabitant) aged 18–55 years participated in the study. Each participant received an Android HTC Sensation 4G smartphone containing a custom application suite of 19 tests capturing participant performance and patient-reported outcomes (PROs). Over 1 year, participants were prompted daily to complete one assigned test. Results: A total of 22 patients with MS and 17 cohabitants completed the entire study. Among patients with MS, low scores on PROs relating to mental and visual function were associated with dropout (p < 0.05). We illustrate several novel features of a smartphone platform. First, fluctuations in MS outcomes (e.g., fatigue) were assessed against an individual's ambient environment by linking responses to meteorological data. Second, both response accuracy and speed for the Ishihara color vision test were captured, highlighting the benefits of both active and passive data collection. Third, a new trait, a person-specific learning curve in neuropsychological testing, was identified using spline analysis. Finally, averaging repeated measures over the study yielded the most robust correlation matrix of the different outcome measures. Conclusions: We report the feasibility of, and barriers to, deploying a smartphone platform to gather useful passive and active performance data at high frequency in an unstructured manner in the field. A smartphone platform may therefore enable large-scale naturalistic studies of patients with MS or other neurologic diseases.
  • Thumbnail Image
    Publication
    Whole Brain Volume Measured from 1.5T versus 3T MRI in Healthy Subjects and Patients with Multiple Sclerosis
    (Wiley-Blackwell, 2015) Chu, Renxin; Tauhid, Shahamat; Glanz, Bonnie; Healy, Brian; Kim, Gloria; Oommen, Vinit V.; Khalid, Fariha; Neema, M; Bakshi, Rohit
    Background: Whole brain atrophy is a putative outcome measure in monitoring relapsing-remitting multiple sclerosis (RRMS). With the ongoing MRI transformation from 1.5T to 3T, there is an unmet need to calibrate this change. We evaluated brain parenchymal volumes (BPVs) from 1.5T versus 3T in MS and normal controls (NC). Methods: We studied MS [n = 26, age (mean, range) 43 (21-55), 22 (85%) RRMS, Expanded Disability Status Scale (EDSS) 1.98 (0-6.5), timed 25 foot walk (T25FW) 5.95 (3.2-33.0 seconds)] and NC [n = 9, age 45 (31-53)]. Subjects underwent 1.5T (Phillips) and 3T (GE) 3-dimensional T1-weighted scans to derive normalized BPV from an automated SIENAX pipeline. Neuropsychological testing was according to consensus panel recommendations. Results: BPV-1.5T was higher than BPV-3T [mean (95% CI) + 45.7 mL (+35.3, +56.1), P < .00001], most likely due to improved tissue-CSF contrast at 3T. BPV-3T showed a larger volume decrease and larger effect size in detecting brain atrophy in MS versus NC [-74.5 mL (-126.5, -22.5), P = .006, d = .92] when compared to BPV-1.5T [-51.3.1 mL (-99.8, -2.8), P = .04, d = .67]. Correlations between BPV-1.5T and EDSS (r = -.43, P = .027) and BPV-3T and EDSS (r = -.49, P = .011) and between BPV-1.5T and T25FW (r = -.46, P = .018) and BPV-3T and T25FW (r = -.56, P = .003) slightly favored 3T. BPV-cognition correlations were significant (P < .05) for 6 of 11 subscales to a similar degree at 1.5T (r range = .44-.58) and 3T (r range = .43-.53). Conclusions: Field strength may impact whole brain volume measurements in patients with MS though the differences are not too divergent between 1.5T and 3T.
  • Thumbnail Image
    Publication
    Identification and Clinical Impact of Multiple Sclerosis Cortical Lesions as Assessed by Routine 3T MR Imaging
    (American Society of Neuroradiology (ASNR), 2011) Mike, A.; Glanz, Bonnie; Hildenbrand, Peter G.; Meier, Dominik; Bolden, K.; Liguori, M.; Dell, E.; Healy, Brian; Bakshi, Rohit; Guttmann, Charles
    Background and Purpose: Histopathologic studies have reported widespread cortical lesions in MS; however, in vivo detection by using routinely available pulse sequences is challenging. We investigated the relative frequency and subtypes of cortical lesions and their relationships to white matter lesions and cognitive and physical disability. Materials and Methods: Cortical lesions were identified and classified on the basis of concurrent review of 3D FLAIR and 3D T1-weighted IR-SPGR 3T MR images in 26 patients with MS. Twenty-five patients completed the MACFIMS battery. White matter lesion volume, cortical lesion number, and cortical lesion volume were assessed. Results: Overall, 249 cortical lesions were detected. Cortical lesions were present in 24/26 patients (92.3%) (range per patient, 0–30; mean, 9.6 ± 8.8). Most (94.4%, n = 235) cortical lesions were classified as mixed cortical-subcortical (type I); the remaining 5.6% (n = 14) were classified as purely intracortical (type II). Subpial cortical lesions (type III) were not detected. White matter lesion volume correlated with cortical lesion number and cortical lesion volume (rS = 0.652, rS = 0.705, respectively; both P < .001). After controlling for age, depression, and premorbid intelligence, we found that all MR imaging variables (cortical lesion number, cortical lesion volume, white matter lesion volume) correlated with the SDMT score (R2 = 0.513, R2 = 0.449, R2 = 0.418, respectively; P < .014); cortical lesion number also correlated with the CVLT-II scores (R2 = 0.542–0.461, P < .043). The EDSS scores correlated with cortical lesion number and cortical lesion volume (rS = 0.472, rS = 0.404, respectively; P < .05), but not with white matter lesion volume. Conclusions: Our routinely available imaging method detected many cortical lesions in patients with MS and was useful in their precise topographic characterization in the context of the gray matter−white matter junction. Routinely detectable cortical lesions were related to physical disability and cognitive impairment.
  • Thumbnail Image
    Publication
    Brain MRI Lesion Load at 1.5T and 3T versus Clinical Status in Multiple Sclerosis
    (Wiley-Blackwell, 2011) Stankiewicz, James; Glanz, Bonnie; Healy, Brian; Arora, A; Neema, M; Benedict, Ralph H.B.; Guss, Zachary D.; Tauhid, Shahamat; Buckle, Guy J.; Houtchens, Maria; Khoury, Samia; Weiner, Howard; Guttmann, Charles; Bakshi, Rohit
    Background/Purpose: To assess correlation between brain lesions and clinical status with 1.5T and 3T magnetic resonance imaging (MRI). Methods: Brain MRI fluid-attenuated inversion-recovery (FLAIR) sequences were performed in 32 multiple sclerosis (MS) patients. Expanded Disability Status Scale (EDSS) score (mean ± standard deviation) was 2 ± 2.0 (range 0-8), disease duration 9.3 ± 8.0 (range .8-29) years. Results: FLAIR lesion volume (FLLV) at 3T was higher than at 1.5T (P= .01). Correlation between 1.5T FLLV and EDSS score was poor, while 3T FLLV correlated moderately and significantly (rs= .39, P= .03). When controlling for age and depression, correlations between FLLV and cognitive measures were significant at 1.5T for the Judgment of Line Orientation test (JLO) (rs=−.44, P= .05), the Symbol Digit Modalities Test (SDMT) (rs=−.49, P= .02), and the California Verbal Learning Test Delayed Free Recall (CVLT DR) (rs=−.44, P= .04). Correlations at 3T were also significant for these tests, but of greater magnitude: JLO (rs=−.70, P= .0005), SDMT (rs=−.73, P= .0001), CVLT DR (rs=−.061, P= .003). Additional significant correlations obtained only at 3T included the 2 second-paced auditory serial addition test (rs=−.55, P= .01), the Brief Visuospatial Memory Test-Delayed Free Recall (rs=−.56, P= .007), and the California Verbal Learning Test Total Recall (rs=−.42, P= .05). Conclusion: MRI at 3T may boost sensitivity and improve validity in MS brain lesion assessment.