Faculty Bibliography
Searched for:
person:herbej01
Total Results:
184
Single-question patient-reported disability strongly correlates with expanded disability status scale [Meeting Abstract]
Objectives: To determine correlation between patient-reported disability as assessed with Patient Determined Disability Steps (PDDS) and clinician-rated Expanded Disability Status Scale (EDSS). Background: The EDSS is the 'gold standard' clinical assessment of disability in MS, but requires a trained examiner and is time-consuming. It would be valuable to have a patient-reported outcome measure for tracking disability that shows a high degree of concordance with EDSS and is easy to deploy in a busy clinic. Methods: Consecutive MS patients at an outpatient MS Center were asked to record their disability on the PDDS scale at routine visits, while a Neurostatus-certified physician assessed EDSS, confirmed MS diagnosis, and documented disease duration, relapse status and current disease-modifying therapy in a standardized fashion. Correlations between PDDS, EDSS and Functional System (FS) scores were computed for all patients using SAS software. EDSS-based MS Severity Score (MSSS) and PDDS-based Patient reported-MS severity Score (P-MSSS) were obtained using published reference Tables and compared. Results: 195 MS patients (age 46.4 +/-12.7 years, range=18-87; 73% female; disease duration 10.2+/- 7.4 years) were included. 82% of patients were on DMTs. 11 patients (5.6%) had a relapse at the time of the visit. Mean PDDS was 2.2 +/-2.4, range 0-7. Mean EDSS was 3.1 +/-2.3, range 0-9. PDDS strongly correlated with the EDSS (r=0.89, p< 0.0001) and P-MSSS correlated with MSSS (r=0.83, p< .0001). PDDS scores differed from the EDSS by 2 points or more in only 7 patients (3.6%). PDDS/EDSS correlation were similar among patients with and without obligate ambulatory assistance (r=0.62 for EDSS< 6 group and r= 0.56 for EDSS>5.5 group) and remained highly significant in patients with a relapse (r=0.84, p< .001). PDDS and EDSS showed strong correlation with pyramidal score (r=0.86 for PDDS and r=0.84 for EDSS) and bladder score (r=0.70 for PDDS and r=0.66 for EDSS); weak-to-moderate correlation (r from 0.3 to 0.6) with cerebellar, brainstem, sensory and cognition FS scores, and no correlation (r< 0.02) with vision score. Conclusions: The single-question PDDS is a reliable, highlyefficient and cost-effective tool for disability assessment in clinical and research settings that shows excellent correlation with the 'gold standard' EDSS
EMBASE:72057847
ISSN: 1352-4585
CID: 1841122
An ImmunoChip study of multiple sclerosis risk in African Americans
The aims of this study were: (i) to determine to what degree multiple sclerosis-associated loci discovered in European populations also influence susceptibility in African Americans; (ii) to assess the extent to which the unique linkage disequilibrium patterns in African Americans can contribute to localizing the functionally relevant regions or genes; and (iii) to search for novel African American multiple sclerosis-associated loci. Using the ImmunoChip custom array we genotyped 803 African American cases with multiple sclerosis and 1516 African American control subjects at 130 135 autosomal single nucleotide polymorphisms. We conducted association analysis with rigorous adjustments for population stratification and admixture. Of the 110 non-major histocompatibility complex multiple sclerosis-associated variants identified in Europeans, 96 passed stringent quality control in our African American data set and of these, >70% (69) showed over-representation of the same allele amongst cases, including 21 with nominally significant evidence for association (one-tailed test P < 0.05). At a further eight loci we found nominally significant association with an alternate correlated risk-tagging single nucleotide polymorphism from the same region. Outside the regions known to be associated in Europeans, we found seven potentially associated novel candidate multiple sclerosis variants (P < 10(-4)), one of which (rs2702180) also showed nominally significant evidence for association (one-tailed test P = 0.034) in an independent second cohort of 620 African American cases and 1565 control subjects. However, none of these novel associations reached genome-wide significance (combined P = 6.3 x 10(-5)). Our data demonstrate substantial overlap between African American and European multiple sclerosis variants, indicating common genetic contributions to multiple sclerosis risk.
PMCID:4553906
PMID: 25818868
ISSN: 1460-2156
CID: 1602622
Non-Gaussian diffusion MRI of gray matter is associated with cognitive impairment in multiple sclerosis
BACKGROUND: Non-Gaussian diffusion imaging by using diffusional kurtosis imaging (DKI) allows assessment of isotropic tissue as of gray matter (GM), an important limitation of diffusion tensor imaging (DTI). OBJECTIVE: In this study, we describe DKI and DTI metrics of GM in multiple sclerosis (MS) patients and their association with cognitive deficits. METHODS: Thirty-four patients with relapsing-remitting MS and 17 controls underwent MRI on a 3T scanner including a sequence for DKI with 30 diffusion directions and 3b values for each direction. Mean kurtosis (MK), mean diffusivity and fractional anisotropy (FA) of cortical and subcortical GM were measured using histogram analysis. Spearman rank correlations were used to characterize associations among imaging measures and clinical/neuropsychological scores. RESULTS: In cortical GM, a significant decrease of MK (0.68 vs. 0.73; p < 0.001) and increase of FA (0.16 vs. 0.13; p < 0.001) was found in patients compared to controls. Decreased cortical MK was correlated with poor performance on the Delis-Kaplan Executive Function System test (r = 0.66, p = 0.01). CONCLUSION: Mean kurtosis is sensitive to abnormality in GM of MS patients and can provide information that is complementary to that of conventional DTI-derived metrics. The association between MK and cognitive deficits suggests that DKI might serve as a clinically relevant biomarker for cortical injury.
PMCID:4429046
PMID: 25392318
ISSN: 1477-0970
CID: 1616022
Higher weight in adolescence and young adulthood is associated with an earlier age at multiple sclerosis onset
BACKGROUND: Growing evidence suggests an association between adolescent obesity and increased risk of multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to investigate whether weight or body mass index (BMI) in adolescence and young adulthood was associated with age at MS symptom onset. METHODS: Our cohort is comprised of a sub-group of 184 women enrolled in the New York State MS Consortium registry. Individuals were asked to recall their weight at the time of first menstruation and at age 25. BMI was calculated accordingly for age 25. Regression analyses were carried out to investigate the association between weight or BMI and age at onset. RESULTS: Weight at menarche was significantly related to younger age at symptom onset (beta = -0.073, p = 0.001). These results were also found at age 25 for weight (beta = -0.080, p < 0.001) and BMI (beta = -0.448, p = 0.001). Significantly earlier disease onset (26.9 years +/-9.9) was observed in individuals who were overweight at 25 compared to those who were not overweight (32.1 years +/-9.2, p = 0.006). CONCLUSIONS: Women who reported higher weight in adolescence and BMI in early adulthood were younger at MS onset. Future research should investigate whether there is a causal link between body weight and MS, as prevention lifestyle and dietary interventions could be implemented.
PMID: 25392327
ISSN: 1477-0970
CID: 2237042
A Case of Encephalopathy in an Immunocompetent Adult with Persistent Parvovirus B19 Viremia
ORIGINAL:0009724
ISSN: 1874-205x
CID: 1632702
Predictors of disability worsening in clinically isolated syndrome
OBJECTIVE: To assess demographic, clinical, magnetic resonance imaging, and treatment exposure predictors of time to 3 or 12-month confirmed disability worsening in clinically isolated syndrome (CIS) and early multiple sclerosis (MS). METHODS: We utilized the MSBase Incident Study (MSBasis), a prospective cohort study of outcome after CIS. Predictors of time to first 3 and 12-month confirmed expanded disability status scale worsening were analyzed using Cox proportional hazards regression. RESULTS: About 1989 patients were analyzed, the largest seen-from-onset cohort reported to-date. A total of 391 patients had a first 3-month confirmed disability worsening event, of which 307 were sustained for 12 months. Older age at CIS onset (adjusted hazard ratio: aHR 1.17, 95% 1.06, 1.30), pyramidal (aHR 1.45, 95% CI 1.13, 1.89) and ambulation (HR 1.60, 95% CI 1.09, 2.34) system dysfunction, annualized relapse rate (aHR 1.20, 95% CI 1.18, 1.22), and lower proportion of observation time on treatment were associated with 3-month confirmed worsening. Predictors of time to 12-month sustained worsening included pyramidal system dysfunction (Hazard ratio: aHR 1.38, 95% CI 1.05, 1.83), and older age at CIS onset (aHR 1.17, 95% CI 1.04, 1.31). Greater proportion of follow-up time exposed to treatment was associated with greater reductions in the rate of worsening. INTERPRETATION: This study provides class IV evidence for a strong protective effect of disease-modifying treatment to reduce disability worsening events in patients with CIS and early MS, and confirms age and pyramidal dysfunction at onset as risk factors.
PMCID:4435703
PMID: 26000321
ISSN: 2328-9503
CID: 1602872
Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study
OBJECTIVE:To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study. METHODS:CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 patients with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 patients (MRI cohort). RESULTS:DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance. CONCLUSIONS:The robust effects on MRI active lesion counts and total lesion volume in patients with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS. CLASSIFICATION OF EVIDENCE/METHODS:This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment.
PMCID:4371413
PMID: 25681448
ISSN: 1526-632x
CID: 5348212
Regional gray matter atrophy in relapsing remitting multiple sclerosis: baseline analysis of multi-center data
Regional gray matter (GM) atrophy in multiple sclerosis (MS) at disease onset and its temporal variation can provide objective information regarding disease evolution. An automated pipeline for estimating atrophy of various GM structures was developed using tensor based morphometry (TBM) and implemented on a multi-center sub-cohort of 1008 relapsing remitting MS (RRMS) patients enrolled in a Phase 3 clinical trial. Four hundred age and gender matched healthy controls were used for comparison. Using the analysis of covariance, atrophy differences between MS patients and healthy controls were assessed on a voxel-by-voxel analysis. Regional GM atrophy was observed in a number of deep GM structures that included thalamus, caudate nucleus, putamen, and cortical GM regions. General linear regression analysis was performed to analyze the effects of age, gender, and scanner field strength, and imaging sequence on the regional atrophy. Correlations between regional GM volumes and expanded disability status scale (EDSS) scores, disease duration (DD), T2 lesion load (T2 LL), T1 lesion load (T1 LL), and normalized cerebrospinal fluid (nCSF) were analyzed using Pearson׳s correlation coefficient. Thalamic atrophy observed in MS patients compared to healthy controls remained consistent within subgroups based on gender and scanner field strength. Weak correlations between thalamic volume and EDSS (r=-0.133; p<0.001) and DD (r=-0.098; p=0.003) were observed. Of all the structures, thalamic volume moderately correlated with T2 LL (r=-0.492; P-value<0.001), T1 LL (r=-0.473; P-value<0.001) and nCSF (r=-0.367; P-value<0.001).
PMCID:4366621
PMID: 25787188
ISSN: 2211-0356
CID: 5348172
Relationship between iron accumulation and white matter injury in multiple sclerosis: a case-control study
Despite the increasing development and applications of iron imaging, the pathophysiology of iron accumulation in multiple sclerosis (MS), and its role in disease progression and development of clinical disability, is poorly understood. The aims of our study were to determine the presence and extent of iron in T2 visible lesions and gray and white matter using magnetic field correlation (MFC) MRI and correlate with microscopic white matter (WM) injury as measured by diffusion tensor imaging (DTI). This is a case-control study including a series of 31 patients with clinically definite MS. The mean age was 39 years [standard deviation (SD) = 9.55], they were 11 males and 20 females, with a disease duration average of 3 years (range 0-13) and a median EDSS of 2 (0-4.5). Seventeen healthy volunteers (6 males and 11 females) with a mean age of 36 years (SD = 11.4) were recruited. All subjects underwent MR imaging on a 3T scanner using T2-weighted sequence, 3D T1 MPRAGE, MFC, single-shot DTI and post-contrast T1. T2-lesion volumes, brain volumetry, DTI parameters and iron quantification were calculated and multiple correlations were exploited. Increased MFC was found in the putamen (p = 0.061), the thalamus (p = 0.123), the centrum semiovale (p = 0.053), globus pallidus (p = 0.008) and gray matter (GM) (p = 0.004) of MS patients compared to controls. The mean lesional MFC was 121 s-2 (SD = 67), significantly lower compared to the GM MFC (<0.0001). The GM mean diffusivity (MD) was inversely correlated with the MFC in the centrum semiovale (p < 0.001), and in the splenium of the corpus callosum (p < 0.001). Patients with MS have increased iron in the globus pallidus, putamen and centrum with a trend toward increased iron in all the brain structures. Quantitative iron evaluation of WM and GM may improve the understanding of MS pathophysiology, and might serve as a surrogate marker of disease progression.
PMCID:4452503
PMID: 25416468
ISSN: 0340-5354
CID: 1359352
Disease exacerbation after rituximab induction in neuromyelitis optica
PMCID:4335814
PMID: 25738163
ISSN: 2332-7812
CID: 1480662
