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Bianca Weinstock-Guttman

Publications and source records attributed to Bianca Weinstock-Guttman.

28 records · Page 2Linked to original sources
PubMed2004

Reliable screening for neuropsychological impairment in multiple sclerosis.

In an earlier study, we developed the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) to assist in the screening for neuropsychological (NP) impairments. Self-report MSNQ scores correlated significantly with measures of depression, whereas informant-report MSNQ scores correlated with cognitive performance, but not depression. This study was criticized for use of a small sample and lack of data regarding normal performance and test-retest reliability. The present study was designed to replicate the earlier work with a larger sample of patients and normal controls obtained from multiple sites. We also evaluated the test-retest reliability and predictive validity of the MSNQ. The sample included 85 multiple sclerosis (MS) patients and 40 normal controls, matched on demographic variables. All participants completed the MSNQ and underwent NP testing. Thirty-four patients were re-examined at one week. Pearson and ANOVA techniques were utilized for univariate comparisons. Bayesian statistics were calculated to assess predictive validity. Patient self- and informant-report MSNQ scores differed from normal and test retest reliability indices were high. Both self- and informant-reports were correlated with cognitive dysfunction and depression scales. Self-report MSNQ scores correlated more strongly with depression than cognitive performance, whereas the opposite pattern was observed with informant-report scores. Bayesian statistics showed that informant-report MSNQ scores predict cognitive impairment and patient self-report scores identify patients with cognitive impairment or depression. It is concluded that the MSNQ is useful, although patient self-reports may be exaggerated in depressed patients or reduced in patients with severe cognitive impairment.

Adult↗
PubMed2004

Risk of bone loss in men with multiple sclerosis.

CONTEXT: Osteoporosis and the increased fracture risk associated with osteoporosis become apparent in men approximately 10 years later than women. However, in recent studies, approximately 20% of healthy men in the age range 55-64 years were found to be osteopenic. Emerging data suggest a significantly increased prevalence of osteoporosis in men and women with multiple sclerosis (MS) compared to age-matched controls, but no specific clinical testing recommendations are available for men. OBJECTIVE: To determine the proportion of male MS patients with osteoporosis and to identify the factors associated with the reduction in bone mass. DESIGN: Consecutive male MS patients seen at our MS clinic were screened with dual-X-ray absorptiometry (DEXA) scan for determining the bone mineral density (BMD). All patients had neurological Expanded Disability Status Scale (EDSS) evaluation. The results were compared to healthy age-matched male reference population using the Z score and to a cohort of women MS patients and women controls. Calcium, total testosterone, sex-hormone binding globulin (SHBG), 25-hydroxy-vitamin-D, and parathyroid hormone (PTH) were evaluated in male patients with decreased BMD. Relevant data on body mass index (BMI), medication, alcohol consumption, smoking, and sexual dysfunction were recorded. SETTING: Academic MS Centre. PATIENTS AND OTHER PARTICIPANTS: Forty consecutive male MS patients, age mean 51.2 +/- 8.7 years, and mean EDSS of 5.8 +/- 1.9 were evaluated with DEXA scan. Of these, 17.5% patients were relapsing-remitting (RR) MS, 57.5% were secondary progressive (SP) MS and 25% were primary progressive (PP) MS. MAIN OUTCOME MEASURE: Proportion of male MS patients with reduced BMD at the lumbar spine and femoral neck. RESULTS: Thirty-two (80%) of our patients had a reduced bone mass of either lumbar spine or the femoral neck; of these 17 patients (42.5%) had osteopenia and 15 patients (37.5%) had osteoporosis. Twenty-one per cent (eight out of 38 patients) had vertebral, rib or extremities fractures. Multivariate linear regression analysis indicated that the EDSS (P < 0.0001) and BMI (P = 0.0004) were the important factors associated with low BMD at the femoral neck and the EDSS was the important factor (P = 0.0017) associated with low BMD at the lumbar spine. The same factors emerged as significantly associated with the corresponding Z scores, which are corrected for age and sex. No clear association between intravenous steroid therapy and BMD was evident in the multivariate analysis. Low levels of 25-hydroxy-vitamin-D were seen in 37.5% of patients. CONCLUSIONS: The proportion of male MS patients with reduced bone mass is high and disproportionate to their age and ambulation, consistent with an association between the MS disease process and pathological bone loss. Increased awareness and bone density screening of male and female MS patients over 40 years of age is warranted.

Absorptiometry, Photon↗
PubMed2004

Combination therapy for multiple sclerosis: the treatment strategy of the future?

Multiple sclerosis (MS) is an inflammatory autoimmune disease characterised by demyelination and axonal loss in the CNS. Although new immunomodulatory therapies including interferon-beta and glatiramer acetate became available during the last decade, these therapies are only partially effective. There is a continuing need to develop more effective treatment strategies to combat the chronic and progressive aspects of the disease. In view of the complex pathophysiology underlying the MS disease process, combination therapy offers a rational therapeutic approach. Combining immunomodulatory agents with different mechanisms of action that promote synergistic or additive effects represents an important objective in MS therapeutic research. Ultimately, the optimal therapies will likely include strategies that promote repair and limit tissue destruction in combination with anti-inflammatory interventions.

Adjuvants, Immunologic↗
PubMed2003

Genomic effects of IFN-beta in multiple sclerosis patients.

The purpose of this report was to characterize the dynamics of the gene expression cascades induced by an IFN-beta-1a treatment regimen in multiple sclerosis patients and to examine the molecular mechanisms potentially capable of causing heterogeneity in response to therapy. In this open-label pharmacodynamic study design, peripheral blood was obtained from eight relapsing-remitting multiple sclerosis patients just before and at 1, 2, 4, 8, 24, 48, 120, and 168 h after i.m. injection of 30 micro g of IFN-beta-1a. The total RNA was isolated from monocyte-depleted PBL and analyzed using cDNA microarrays containing probes for >4000 known genes. IFN-beta-1a treatment resulted in selective, time-dependent effects on multiple genes. The mRNAs for genes implicated in the anti-viral response, e.g., double-stranded RNA-dependent protein kinase, myxovirus resistance proteins 1 and 2, and guanylate binding proteins 1 and 2 were rapidly induced within 1-4 h of IFN-beta treatment. The mRNAs for several genes involved in IFN-beta signaling, such as IFN-alpha/beta receptor-2 and Stat1, were also increased. The mRNAs for lymphocyte activation markers, such as IFN-induced transmembrane protein 1 (9-27), IFN-induced transmembrane protein 2 (1-8D), beta(2)-microglobulin, and CD69, were also increased in a time-dependent manner. The findings demonstrate that IFN-beta treatment induces specific and time-dependent changes in multiple mRNAs in lymphocytes of multiple sclerosis patients that could provide a framework for rapid monitoring of the response to therapy.

Adult↗
PubMed2003

Sex differences in in vitro pro-inflammatory cytokine production from peripheral blood of multiple sclerosis patients.

We compared the patterns of the pro-inflammatory cytokines, interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha), and the anti-inflammatory cytokines, interleukin-10 (IL-10) and tumor growth factor-beta (TGF-beta) from peripheral blood of male and female patients with relapsing-remitting (RR) and secondary progressive (SP) forms of multiple sclerosis (MS). The relationships between pro-inflammatory cytokines and disability (expanded disability status scale, EDSS) were also examined. Peripheral blood anti-coagulated with heparin was obtained from 47 MS patients (30 women and 17 men) and activated with phorbol-12-myristate 13 acetate (PMA) and ionomycin in the presence of brefeldin A and stained for flow cytometry with fluorescently labeled antibodies against intracellular IFN-gamma, TNF-alpha, IL-2, IL-4 and IL-10. The T cells were delineated with peridinin chlorophyll protein (Per-CP) labeled anti-CD3 antibody. The stained samples were analyzed on a flow cytometer to assess the intracellular pro-inflammatory cytokine patterns. The levels of interleukin-10 (IL-10) and tumor growth factor-beta (TGF-beta) were measured in plasma using enzyme-linked immunoassay. The percentage of TNF-alpha-producing CD3 positive cells was significantly higher (P=0.045) in men (mean+/-S.D., 39+/-13%) than in women (mean+/-S.D., 29+/-13%) RR-MS patients. The percentage of CD3 positive cells producing IFN-gamma was significantly correlated with EDSS in females but not in males (Spearman rank correlation r(S)=0.49, P=0.018). The secretion of the pro-inflammatory cytokines, IFN-gamma and TNF-alpha, is influenced by gender in MS patients and may contribute to the sexual dimorphism of MS.

Adolescent↗
PubMed2003

Dynamics of immune cell trafficking in interferon-beta treated multiple sclerosis patients.

PURPOSE: To investigate the effects of interferon-beta-1a (IFN-beta-1a) on the trafficking of cell populations in peripheral blood cells of multiple sclerosis (MS) patients. METHODS: In this open-label pharmacodynamic study, peripheral blood was obtained from 10 relapsing-remitting (RR) MS patients just prior to and at 1, 2, 4, 8, 24, 48, 120, and 168 h after intramuscular injection of 30-microg IFN-beta-1a. Timed samples were also obtained from five controls at 0, 8, 24, 48 and 168 h. The blood cells were analyzed using four-color flow cytometry with antibody conjugates directed against cell surface proteins specific for T cells, B cells, NK cells, and the activation marker, CD69. RESULTS: IFN-beta-1a treatment resulted in selective, time-dependent effects on many cell populations in peripheral blood. The trafficking of T-helper and T-suppressor/cytotoxic subsets of T cells were qualitatively different. The most prominent effects were on the trafficking of natural killer cells, the levels of which decreased to 23.5% of pretreatment values at 8 h after treatment. The levels of CD69-positive NK cells increased to a peak value of 606% of pretreatment levels at the 24-h time point. In untreated controls, these characteristic trafficking effects were not observed. There was inter-patient heterogeneity in the levels of activated NK cells at the 6-month time point that may potentially be relevant for individualizing IFN-beta therapy. CONCLUSIONS: IFN-beta treatment can induce specific, selective, and time-dependent trafficking of cells and its effects on different subsets of a given cell type are not qualitatively similar. The dynamics indicate that the activation of NK cells by IFN-beta is possibly dependent on the trafficking of NK cells. The activated NK cell levels after prolonged therapy may potentially provide a surrogate marker for IFN-beta exposure.

Adjuvants, Immunologic↗
PubMed2003

Factors that predict health-related quality of life in patients with relapsing-remitting multiple sclerosis.

Health-Related Quality of Life (HRQoL) research is gaining acceptance in the field of multiple sclerosis (MS). Little is known about what precipitates quality of life change. It was hypothesized that physical aspects of quality of life decline with worsening objective disease measures and psychosocial aspects remain relatively stable regardless of change in objective measures. These assumptions are tested using data from a Phase 3 study of relapsing-remitting MS patients treated with interferon beta-1a and reassessed approximately eight years after study initiation. The Sickness Impact Profile (SIP) questionnaire is the generic quality of life measure used in this study. Three summary scores of the SIP (Physical, Psychosocial, and Total scores), Expanded Disability Status Scores, Multiple Sclerosis Functional Composite, and Brain Parenchymal Fraction were determined at baseline, year 2, and after an average of 8.1 years from study entry. SIP data collected during a clinic visit were available from 137 of the original 172 participants. All objective indicators worsened by follow-up. SIP Physical and Total scores significantly worsened from baseline to follow-up. SIP Psychosocial showed nonsignificant worsening. Regression analysis indicated that final measures of SIP Physical and Total scores were most strongly associated with change in objective measures and follow-up SIP Psychosocial was most strongly related to earlier scores on the same measure.

Adjuvants, Immunologic↗
PubMed2003

Thalamic involvement in multiple sclerosis: a diffusion-weighted magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Injury to deep gray matter structures in multiple sclerosis (MS) has been suggested by recent neuro-imaging and neuropathology studies. Diffusion-weighted magnetic resonance imaging (MRI) can assess tissue damage with greater sensitivity than conventional MRI. The authors' objective was to assess thalamic gray matter damage by diffusion-weighted imaging in MS patients. METHODS: This was a retrospective study performed at a tertiary care, university-affiliated comprehensive MS center of 82 MS patients and 43 controls. The main outcome measures were thalamic apparent diffusion coefficients (ADCs), whole-brain atrophy (brain parenchymal fraction), fluid-attenuated inversion recovery (FLAIR) hypertense lesion volume, and clinical course. RESULTS: ADCs in the left thalamus were higher in MS patients (0.741 +/- 0.044 x 10(-3) mm2/s) than controls (0.723 +/- 0.036 x 10(-3) mm2/s) (P = .027) and higher in secondary progressive MS patients (0.761 +/- 0.044 x 10(-3) mm2/s) than relapsing-remitting MS patients (0.735 +/- 0.032 x 10(-3) mm2/s) (P = .029). ADCs in the right thalamus were higher in secondary progressive MS patients (0.784 +/- 0.069 x 10(-3) mm2/s) than controls (0.757 +/- 0.038 x 10(-3) mm2/s) (P = .033). In the MS group, left thalamus ADCs correlated negatively with brain parenchymal fraction (r = -0.30, P = .008), total left hemispheric FLAIR lesion volume correlated with ADCs in the left (r = 0.35, P = .001) and right (r = 0.39, P < .001) thalami, and total right hemispheric FLAIR lesion volume correlated with ADCs in the left (r = 0.31, P = .006) and right thalami (r = 0.22, P = .048). CONCLUSION: MS patients have increased water diffusion in the thalamus that is partly associated with clinical course, lesion load, and whole-brain atrophy. Both indirect and direct mechanisms of gray matter injury may play a role in the pathophysiology of MS.

Adult↗
PubMedDate not supplied

Whole-brain atrophy in multiple sclerosis measured by automated versus semiautomated MR imaging segmentation.

BACKGROUND AND PURPOSE: Semiautomated and automated methods are used to measure whole-brain atrophy in multiple sclerosis (MS), but their comparative reliability, sensitivity, and validity are unknown. METHODS: Brain parenchymal fraction (BPF) was measured in patients with MS (n = 52) and healthy control subjects (n = 17) by four methods: semiautomated or automated segmentation and 2D or 3D pulse sequences. Linear measures of atrophy, whole-brain lesion volumes, and clinical data were used to explore validity. RESULTS: The 2D automated method yielded unreliable segmentation and was discarded. The three other BPF methods produced data that were highly intercorrelated and indistinguishable by analysis of variance. In the MS group, semiautomated (2D: 0.84 +/- 0.04, P <.001; 3D: 0.84 +/- 0.05, P =.04) and automated 3D (0.83 +/- 0.05, P =.002) BPFs were lower than controls (semiautomated 2D: 0.88 +/- 0.02; 3D: 0.88 +/- 0.03; automated 3D: 0.88 +/- 0.03). In the MS group, the semiautomated (r = -.79 to -.82) and automated 3D (r = -.81) BPFs inversely correlated with third ventricular width and showed similarly robust correlations with the bicaudate ratio (all r = -.74). The semiautomated and automated BPFs showed similar, moderate correlations with T1 hypointense and FLAIR hyperintense lesion volume, physical disability (Expanded Disability Status Scale) score, and disease duration and similar differences between secondary progressive and relapsing-remitting patients. The intraobserver, interobserver, and test-retest reliability was somewhat higher for the automated than for the semiautomated methods. CONCLUSION: These automated and semiautomated measures of whole-brain atrophy provided similar and nearly interchangeable data regarding MS. They discriminated MS from healthy individuals and showed similar relationships to established disease variables.

Adult↗