Biomedical subjects

B Weinstock-Guttman

Publications and source records attributed to B Weinstock-Guttman.

At least 19 recordsLinked to original sources

PubMed2006

Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis.

Grey matter hypointensity on T2-weighted magnetic resonance imaging (MRI) scans, suggesting iron deposition, has been described in multiple sclerosis (MS) and is related to physical disability, disease course and brain atrophy. We tested the hypothesis that subcortical grey matter T2 hypointensity is related to cognitive impairment after adjusting for the effect of MRI lesion and atrophy measures. We studied 33 patients with MS and 14 healthy controls. Normalized T2 signal intensity in the caudate, putamen, globus pallidus and thalamus, total brain T1-hypointense lesion volume (T1LV), fluid-attenuated inversion-recovery-hyperintense lesion volume (FLLV) and brain parenchymal fraction (BPF) were obtained quantitatively. A neuropsychological composite score (NCS) encompassed new learning, attention, working memory, spatial processing and executive function. In each of the regions of interest, the normalized T2 intensity was lower in the MS versus control group (all P<0.001). Regression modelling tested the relative association between all MRI variables and NCS. Globus pallidus T2 hypointensity was the only variable selected in the final model (R2 = 0.301, P = 0.007). Pearson correlations between MRI and NCS were T1LV: r = -0.319; FLLV: r = -0.347; BPF: r = 0.374; T2 hypointensity of the caudate: r = 0.305; globus pallidus: r = 0.395; putamen: r = 0.321; and thalamus: r = 0.265. Basal ganglia T2 hypointensity and BPF demonstrated the strongest associations with cognitive impairment on individual cognitive subtests. Subcortical grey matter T2 hypointensity is related to cognitive impairment in MS, supporting the clinical relevance of T2 hypointensity as a biological marker of MS tissue damage. These data implicate a role for basal ganglia iron deposition in neuropsychological dysfunction.

Adult↗

PubMed2005

MRI T2 hypointensity of the dentate nucleus is related to ambulatory impairment in multiple sclerosis.

OBJECTIVES: MRI T2 hypointensity in multiple sclerosis (MS) gray matter, suggesting iron deposition, is associated with physical disability, disease course, lesion load, and brain atrophy. Ambulatory dysfunction limits quality of life; however correlation with conventional MRI remains poor. METHODS: Normalized intensity on T2-weighted images was obtained in the basal ganglia, thalamus, red nucleus, and dentate nucleus in 47 MS patients and 15 healthy controls. Brain T1-hypointense and FLAIR-hyperintense lesion volume, third ventricle width, brain parenchymal fraction and timed 25 foot walk (T25FW) were measured in the MS group. RESULTS: T2 hypointensity was present throughout gray matter in MS vs. controls (all p<0.01). Dentate T2 hypointensity was the only MRI variable significantly correlated with T25FW (Pearson r=-0.355, p=0.007) and was also the best MRI correlate of physical disability (EDSS) score in regression modeling (r=-0.463, R(2)=0.223, p=0.004). CONCLUSIONS: T2 hypointensity is present in subcortical gray matter nuclei in patients with MS vs. normal controls. Dentate nucleus T2 hypointensity is independently related to ambulatory impairment and disability, accounting for more variance than conventional lesion and atrophy measures. This study adds more weight to the notion that T2 hypointensity is a clinically relevant marker of tissue damage in MS.

Adult↗

PubMed2005

Low-contrast letter acuity testing captures visual dysfunction in patients with multiple sclerosis.

OBJECTIVE: To evaluate concurrent and predictive validity for low-contrast letter acuity (L-CLA) testing as a candidate visual component for the Multiple Sclerosis Functional Composite (MSFC). METHODS: L-CLA testing was conducted in two MS patient cohorts. In the MSFC Validation Study, 137 participants from a Phase III trial of inteferon beta-1a (Avonex) for relapsing-remitting MS were followed. A second cohort included 65 patients with secondary progressive MS who participated in a substudy of the International MS Secondary Progressive Avonex Controlled Trial (IMPACT). The total number of letters read correctly at four contrast levels (100, 5, 1.25, and 0.6%) was correlated with Expanded Disability Status Scale (EDSS), MSFC, Sickness Impact Profile, Multiple Sclerosis Quality of Life Inventory, and brain parenchymal fraction (BPF), as determined by MRI. RESULTS: Low- and high-contrast letter acuity scores correlated with BPF at follow-up in the MSFC Validation Study (5%: r = 0.40, p < 0.0001; 100%: r = 0.31, p = 0.0002). L-CLA also correlated with EDSS (5%: r = -0.35, p < 0.0001; 1.25%: r = -0.26, p = 0.0003) and MSFC (5%: r = 0.47, p < 0.0001; 1.25%: r = 0.45, p < 0.0001). In the IMPACT Substudy, change in L-CLA scores from baseline to year 1 predicted subsequent change in the EDSS from year 1 to 2 at the 5% (p = 0.0142) and the 1.25% (p = 0.0038) contrast levels, after adjusting for change in MSFC scores from baseline to year 1. CONCLUSIONS: Low-contrast letter acuity (L-CLA) scores demonstrate concurrent and predictive validity in patients with relapsing-remitting and secondary progressive multiple sclerosis (MS). L-CLA testing provides additional information relevant to the MS disease process that is not entirely captured by the Multiple Sclerosis Functional Composite.

Adult↗

PubMed2005

Interpreting patient/informant discrepancies of reported cognitive symptoms in MS.

Although numerous studies have shown that brain-damaged patients tend to underestimate neuropsychological (NP) impairment when self-ratings are compared to informant ratings, the meaning of such discrepancies is not well studied in multiple sclerosis (MS). We compared patient self- and informant-report questionnaire ratings of NP functioning in 122 MS patients and 37 age- and education-matched normal controls. In addition to completing the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ), participants underwent NP testing and assessment of depression, personality, and neuropsychiatric symptoms. Based on the normal distribution of discrepancy scores, patients were classified according to whether they overestimated or underestimated their cognitive ability, relative to informant ratings. ANOVAs comparing test scores derived from overestimators, underestimators, and accurate estimators were significant for multiple measures of cognitive function, depression, personality, and neuropsychiatric symptoms. Overestimators were characterized by less depression and conscientiousness, and greater degrees of cognitive impairment, euphoric behavioral disinhibition, and unemployment as compared to underestimators. We conclude that patient/informant discrepancy scores on the MSNQ are associated with the aforementioned neuropsychiatric features, and that the MSNQ has potential utility for predicting euphoria and disinhibition syndromes in MS.

Adult↗

PubMed2005

Estimating long-term effects of disease-modifying drug therapy in multiple sclerosis patients.

Two methods were used to estimate the long-term impact of disease-modifying drug therapy (DMDT) in patients with relapsing multiple sclerosis (MS) who completed a placebo-controlled, randomized clinical trial of interferon beta-1a (IFNbeta-1a). The study cohort consisted of patients with ambulatory relapsing MS who had previously participated in a placebo-controlled clinical trial for two years. At its end, patients were managed in an unstructured fashion by their neurologists and re-evaluated at an average of 6.1 years after the end of the trial. Follow-up evaluation was obtained for 93% of the 172 eligible patients. Because study inclusion criteria required that all patients have an Expanded Disability Status Scale (EDSS) score of < or = 3.5 at entry, disability progression at follow-up was defined as EDSS > or = 6.0. Two methods were used to estimate the expected proportions that reached EDSS > or = 6.0 at follow-up. Estimates were compared with observed proportions. Method 1 used progression rates observed during the two-year phase III clinical trial and the percentage of time that patients were on DMDT during the follow-up period. Method 2 used progression rates from a natural history comparison group of relapsing-remitting MS patients. At the eight-year follow-up, 42.0% of the original placebo patients and 29.1% of the original IFNbeta-1a patients reached an EDSS > or = 6.0, an observed treatment effect of approximately 30%. Using method 1, it was estimated that 36.3% of the original placebo patients and 27.6% of the original IFNbeta-1a patients should have reached an EDSS > or = 6.0. Use of the natural history control group (method 2) predicted less plausible outcomes. Estimated proportions of patients reaching the endpoint were 63.3% for the original placebo group and 55.8% for the original IFNbeta-1a group. Treatment effect sizes of 75-90% would be required to match estimates from method 2 with the observed outcome. The paucity of data on the long-term treatment of patients with MS may be aided by applying these or similar methods to vigorously followed cohorts of patients.

Adjuvants, Immunologic↗

PubMed2005

A randomized blinded trial of combination therapy with cyclophosphamide in patients-with active multiple sclerosis on interferon beta.

OBJECTIVE: To evaluate the efficacy and safety of combination therapy with pulse cyclophosphamide given with methylprednisolone (MP) and interferon beta (IFNbeta)-Ia in multiple sclerosis (MS) patients with active disease during IFNbeta monotherapy. METHODS: This was a randomized, single-blind, parallel-group, multicenter trial in MS patients with a history of active disease during IFNbeta treatment. Patients were randomized to either cyclophosphamide 800 mg/m2 plus methylprednisolone 1 g IV (CY/MP) or methylprednisolone once a month for six months and then followed for an additional 18 months. All patients received three days of methylprednisolone 1 g IV at screening and 30 mcg IFNbeta-Ia IM weekly for the entire 24 months. The primary endpoint was change from baseline in the mean number of gadolinium-enhancing (Gd+) lesions. Secondary clinical endpoints included time to treatment failure. RESULTS: Fifty-nine patients were randomized to treatment: 30 to CY/MP and 29 to MP Change from baseline in the number of Gd+ lesions was significantly different between treatment groups at three (P =0.01), six (P =0.04) and 12 months (P =0.02), with fewer lesions in the CY/MP group. The cumulative rate of treatment failure was significantly lower in the CY/MP group compared with the MP group (rate ratio =0.30; 95% confidence interval, 0.12-0.75; P =0.011). CY/MP treatment was well tolerated. CONCLUSION: Combination therapy with CY/MP and IFNbeta-Ia decreased the number of Gd+ lesions and slowed clinical activity in patients with previously active disease on IFNbeta alone.

Adjuvants, Immunologic↗

PubMed2004

Clinical characteristics of African Americans vs Caucasian Americans with multiple sclerosis.

BACKGROUND: African American (AA) individuals are thought to develop multiple sclerosis (MS) less frequently than Caucasian American (CA) individuals. OBJECTIVE: To compare the clinical characteristics of AA and CA patients with MS. METHODS: The clinical features of MS were compared in a large retrospective cohort of AA (n = 375) and CA (n = 427) subjects. RESULTS: The proportion of women to men was similar in AA and CA subjects (81% [AA] vs 77% [CA]; p = 0.122). There were no differences in the proportions of subjects with relapsing-remitting, secondary progressive, primary progressive, and progressive relapsing MS. The median time to diagnosis was 1 year after symptom onset in AA subjects and 2 years after symptom onset in CA subjects (p = 0.0013). The age at onset was approximately 2.5 years later in AA than CA subjects (33.7 vs 31.1 years; p = 0.0001). AA subjects presented with multisite signs and symptoms at disease onset more often than CA subjects (p = 0.018). Clinical involvement restricted to the optic nerves and spinal cord (opticospinal MS) occurred in 16.8% of AA patients compared with 7.9% of CA patients (p < 0.001). Transverse myelitis also occurred more frequently in AA subjects (28 vs 18%; p = 0.001). Survival analysis revealed that AA subjects were at higher risk for development of ambulatory disability than CA subjects. After adjusting for baseline variations and differences in therapeutic interventions, AAs were at 1.67-fold greater risk for requiring a cane to ambulate than CA patients (p < 0.001). There was a trend suggesting that AAs were also at greater risk for development of wheelchair dependency (p = 0.099). Adjusted Cox proportional hazard models showed that this effect was in part attributable to the older age at onset in AAs (p < 0.001). CONCLUSIONS: Compared with multiple sclerosis (MS) in Caucasian Americans, African American patients with MS have a greater likelihood of developing opticospinal MS and transverse myelitis and have a more aggressive disease course.

Adult↗

PubMed2004

Multiple sclerosis gender issues: clinical practices of women neurologists.

Substantially more women than men develop multiple sclerosis (MS), but information about the effects of MS and gender-specific issues such as pregnancy, breastfeeding, menstruation and hormone use is lacking. A survey study of neurologists' practice patterns was undertaken to elicit information about gender-specific topics and the use of disease-modifying MS therapies (DMT) including the interferons and glatiramer acetate (GA). A total of 147 surveys were returned. Half of respondents require patients to discontinue DMT during pregnancy, while 35% encourage discontinuation. Among those who allow patients to continue therapy, half consider GA to be safer during pregnancy than the interferons. Nearly 86% of respondents do not use DMT in patients who are breastfeeding. Among the 11% who actually prescribe during breastfeeding, most recommend GA. Neurologists generally leave the decision to breastfeed up to patients, and most refer patients to obstetrician/gynaecologists for counselling about contraception or hormone replacement therapy. The survey results described here provide insight into how neurologists manage reproductive health issues among women with MS.

Breast Feeding↗

PubMed2003

Validity of the Beck Depression Inventory-Fast Screen in multiple sclerosis.

INTRODUCTION: The Beck Depression Inventory-Fast Screen (BDI-FS) is a brief self-report inventory designed to evaluate depression in patients with medical illness. As depressive disorder is especially prominent in multiple sclerosis (MS), a cost-effective procedure for identifying depressive disorder in MS is sorely needed. The BDI-FS may be useful in this regard although, to date, its validity in MS patients has not been assessed. METHODS: Fifty-four consecutive MS patients were studied. All underwent psychological assessment, which included the BDI-FS and other self-report measures of depression. Forty-eight caregiver/informants were interviewed using the Neuorpsychiatric Inventory (NPI). Retrospective chart reviews were conducted by a single trained research assistant, blind to the results of psychological testing and interviews, to determine if antidepressant medications had been prescribed. RESULTS: The BDI-FS was significantly correlated with other self-report measures of depression (P < 0.001) and with informant reported dysphoria (P < 0.01), In addition, BDI-FS scores discriminated MS patients undergoing treatment for depressive disorder from untreated MS patients (P = 0.01). CONCLUSION: These data support the concurrent and discriminative validity of the BDI-FS in MS. As the test is brief and not confounded with neurological symptoms, it is recommended for depression screening in this population.

Adult↗

PubMed2003

Multiple sclerosis characteristics in African American patients in the New York State Multiple Sclerosis Consortium.

The objective of this study was to determine the clinical characteristics of multiple sclerosis (MS) in African American (AA) patients in the New York State Multiple Sclerosis Consortium (NYSMSC) patient registry. The NYSMSC is a group of 18 MS centers throughout New York State organized to prospectively assess clinical characteristics of MS patients. AAs comprise 6% (329) of the total NYSMSC registrants (5602). Demographics, disease course, therapy, and socioeconomic status were compared in AA registrants versus nonAfrican Americans (NAA). There was an increased female preponderance and a significantly younger age at diagnosis in the AA group. AA patients were more likely to have greater disability with increased disease duration. No differences were seen in types of MS and use of disease modifying therapies. Our findings suggest a racial influence in MS. Further genetic studies that consider race differences are warranted to elucidate mechanisms of disease susceptibility.

Adult↗

PubMed2003

Pattern reversal visual evoked potentials as a measure of visual pathway pathology in multiple sclerosis.

BACKGROUND: Pattern reversal visual evoked potentials (PRVEPs) have a well-documented role in diagnosis of multiple sclerosis (MS), but their value as a visual function surrogate remains controversial. METHODS: We evaluated PRVEP in 37 patients with MS who were participating in a long-term follow-up study following a phase III trial of interferon beta-1a (Avonex). Patients were examined to determine the Kurtzke Extended Disability Status Score (EDSS), multiple sclerosis functional composite (MSFC), contrast letter acuity (CLA), and had cranial MRI scans to determine whole brain atrophy (BPF). PRVEP was evaluated for P100 latency, amplitude, and waveform morphology. Two summary scores were created: for Score A, abnormal latencies, morphologies, and amplitudes of each individual eye were added; for Score B, abnormal latencies, morphologies, and amplitude ratio between eyes was determined. Sixteen patients in this group also had PRVEP at the time they enrolled in the clinical trial, eight years previously. RESULTS: At the follow-up exam, over 75% of patients had abnormal PVEP parameters while visual acuity (VA) was abnormal only in 59%. Increased PRVEP latency over the eight-year period correlated with deterioration assessed by EDSS (P = 0.006), BPF (P = 0.0001), and MSFC (P = 0.0041). Score A was significantly correlated with EDSS, BPF, CLA, cognitive function, and quality of life assessed with the Sickness Impact profile. No correlation was seen with the MSFC. CONCLUSIONS: The results indicate that PRVEP measures MS-related pathology, and can provide not only diagnostic but also prognostic information during evaluation of MS patients.

Evoked Potentials, Visual↗

PubMed2002

Eight-year follow-up study of brain atrophy in patients with MS.

OBJECTIVE: To characterize whole-brain atrophy in relapsing-remitting MS (RRMS) patients over an 8-year period. The specific goals of this study were to determine if brain atrophy is related to subsequent disability status and to identify MRI correlates of atrophy progression. METHODS: A follow-up study was conducted to reassess patients from a phase III trial of interferon beta-1a (IFNbeta-1a) 8 years after randomization. Clinical and MRI data from 172 patients followed over 2 years in the original trial were used as baseline data. Follow-up data were obtained on 160 patients, including 134 patients with follow-up MRI examinations. Brain atrophy was estimated by automated calculation of brain parenchymal fraction. The relation between atrophy during the original trial and disability status at follow-up was determined. Correlations were also determined between lesion measurements from the original trial and the brain parenchymal fraction at follow-up. RESULTS: Brain atrophy was correlated with subsequent disability status. Atrophy rate during the original trial was the most significant MRI predictor of disability status at follow-up. Brain atrophy at follow-up was related to lesion volumes measured during the original trial. CONCLUSIONS: The relation between atrophy progression and subsequent neurologic disability status suggests that atrophy progression during RRMS is clinically relevant. Therefore, atrophy progression may be a useful marker for disease progression in clinical trials. The relation between lesions and subsequent atrophy indicates that brain atrophy may be related to focal tissue damage at earlier points in time, but important predisposing or other factors contributing to atrophy remain undefined.

Adjuvants, Immunologic↗

PubMed2002

Cyclophosphamide for multiple sclerosis.

BACKGROUND: Multiple sclerosis is a presumed cell-mediated autoimmune disease of the central nervous system. Cyclophosphamide (CFX) is a cytotoxic and immunosuppressive agent, used in systemic autoimmune diseases. Controversial results have been reported on its efficacy in MS. We conducted a systematic review of all relevant trials, evaluating the CFX efficacy in patients with progressive MS. OBJECTIVES: The main objectives were to determine whether CFX slows the disease progression. SEARCH STRATEGY: Electronic databases (including MEDLINE, EMBASE, Cochrane Controlled Trials Register) were systematically searched. References list of retrieved studies and conference abstracts on the main meetings on Multiple Sclerosis were handsearched. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating the clinical effect of CFX treatment in patients affected by clinically definite progressive MS. CFX had to be administered alone or in combination with ACTH or steroids. The comparison group had to be placebo or no treatment or the same co intervention (ACTH or steroids) The main outcome criteria were : progression of disability (defined as an increase of 0.5 point in Kurtzke Extended Disability Status Scale (EDSS) for patients with baseline EDSS > or = 6 and 1 for EDSS < or = 5.5), differences of disability between treatment-control groups and the number of patients with side effects. DATA COLLECTION AND ANALYSIS: The identified references were reviewed by two reviewers who independently decided the eligibility of the study, extracted and summarized data and assessed the trial's quality. The statistical analysis was performed using the Cochrane RevMan software and analyzed using Cochrane MetaView. MAIN RESULTS: Of the 326 identified references, 80 were selected for full review, only four RCTs were selected for the final analysis. Intensive immunosuppression with CFX (alone or associated with ACTH or prednisone) in patients with progressive MS compared to placebo or no-treatment (152 participants) did not prevent the long -term (12-18-24 months) risk to evolution to a next step of EDSS. However, the mean change in disability (final disability subtracted from the baseline) significantly favoured the treated group at 12 (effect size - 0.21; C. I. - 0.24, - 0.17) and 18 months (- 0.19; C. I. - 0.24, - 0.14). We were not able to verify the efficacy of other schedules. Five patients died; sepsis and amenorrhea frequently occurred in treated patients (descriptive analysis). REVIEWER'S CONCLUSIONS: Only limited objectives were reached. This review shows a role of CFX in the treatment of progressive MS, but less toxic schedules must be considered, before its use in the clinical practice.

Cyclophosphamide↗

PubMed2001

In vivo gene expression revealed by cDNA arrays: the pattern in relapsing-remitting multiple sclerosis patients compared with normal subjects.

OBJECTIVES: To use DNA arrays to identify differences in gene expression associated with relapsing-remitting (RR) MS. METHODS: Total RNA was isolated from monocyte depleted peripheral blood mononuclear cells of 15 RR MS patients and 15 age- and sex-matched controls. The RNA was reverse transcribed to radiolabeled cDNA and the resultant cDNA was used to probe a DNA array containing over 4000 named human genes. The binding of radiolabeled cDNA to the probes on the array was measured by phosphorimager. RESULTS: Of more than 4000 genes tested, only 34 were significantly different in RR-MS patients from controls. Of these, 25 were significantly increased and 9 significantly decreased in the RR MS patients. Twelve of these genes have inflammatory and/or immunological functions that could be relevant to the MS disease process. The potentially relevant genes that were elevated (15% to 28%) were P protein, LCK, cAMP responsive element modulator, IL-7 receptor, matrix metalloproteinase-19, M130 antigen, and peptidyl-prolyl isomerase. Those that were significantly decreased (15% to 35%) were SAS transmembrane 4 superfamily protein, STRL22 (C-C chemokine receptor 6), AFX protein, DNA fragmentation factor-45 and immunoglobulin gamma 3 (Gm marker). CONCLUSIONS: The RR-MS disease effect was relatively restricted and most of the mRNAs tested were not different from the normal controls. However, there were significant differences identified in the expression of a subset of mRNAs, including 13 with inflammatory/immune functions that could be relevant to MS. The systematic use of DNA arrays can provide insight into the dynamic cellular pathways involved in MS pathogenesis and its phenotypic heterogeneity.

Adult↗

PubMed2001

Use of the Multiple Sclerosis Functional Composite to predict disability in relapsing MS.

OBJECTIVE: To determine whether the MS Functional Composite (MSFC) can predict future disease progression in patients with relapsing remitting MS (RR-MS). BACKGROUND: The MSFC was recommended by the Clinical Outcomes Assessment Task Force of the National MS Society as a new clinical outcome measure for clinical trials. The MSFC, which contains a test of walking speed, arm dexterity, and cognitive function, is expressed as a single score on a continuous scale. It was thought to offer improved reliability and responsiveness compared with traditional clinical MS outcome measures. The predictive value of MSFC scores in RR-MS has not been determined. METHODS: The authors conducted a follow-up study of patients with RR-MS who participated in a phase III study of interferon beta-1a (AVONEX) to determine the predictive value of MSFC scores. MSFC scores were constructed from data obtained during the phase III trial. Patients were evaluated by neurologic and MRI examinations after an average interval of 8.1 years from the start of the clinical trial. The relationships between MSFC scores during the clinical trial and follow-up status were determined. RESULTS: MSFC scores from the phase III clinical trial strongly predicted clinical and MRI status at the follow-up visit. Baseline MSFC scores, and change in MSFC score over 2 years correlated with both disability status and the severity of whole brain atrophy at follow-up. There were also significant correlations between MSFC scores during the clinical trial and patient-reported quality of life at follow-up. The correlation with whole brain atrophy at follow-up was stronger for baseline MSFC than for baseline EDSS. CONCLUSION: MSFC scores in patients with RR-MS predict the level of disability and extent of brain atrophy 6 to 8 years later. MSFC scores may prove useful to assign prognosis, monitor patients during early stages of MS, and to assess treatment effects.

Adult↗

PubMed2000

A meta-analysis of methylprednisolone in recovery from multiple sclerosis exacerbations.

Despite recent advances in multiple sclerosis treatment, patients experience relapses for which standard treatment remains glucocorticosteroids (GCS). However, there is limited information comparing doses or routes of administration for different GCS types or the benefit of GCS compared to natural recovery. Currently, high dose (HD) methylprednisolone (MP) is the preferred therapy. We conducted meta-analyses of published studies assessing MP at different doses and in comparison to other steroid products or no treatment. Relevant studies were identified through predetermined processes and five articles met the inclusion criteria. Three studies compared HD MP to placebo; two studies compared the effect of HD MP and low dose (LD) MP; only one accepted report compared HD MP to another GCS. This report could not be included in a meta-analysis. The meta-analysis of HD MP vsplacebo studies indicated a mean treatment difference of 0.76 in Expanded Disability Status Score (EDSS) changes from baseline. The meta-analysis of HD and LD MP demonstrated no difference in EDSS change. Despite these rather obvious findings, these meta-analyses have been valuable in identifying further research questions. We recommend studies to determine optimum benefit related to dosage, timing for starting therapy and the most appropriate GCS type. Given the advances in MS therapeutics, these studies will have to include patients on additional disease modifying therapy. Multiple Sclerosis (2000) 6 267 - 273

Disability Evaluation↗

PubMed2000

Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients.

Brain atrophy measurement can provide an estimate of the amount of tissue destruction due to the pathologic processes in multiple sclerosis. The potential usefulness of atrophy as a marker of disease progression depends upon the concurrent and predictive relationships between atrophy and disability. A follow-up study was performed to measure atrophy and disability scores in patients from the Multiple Sclerosis Collaborative Research Group's phase III trial of IFNbeta-1a (Avonex) in relapsing- remitting multiple sclerosis. New data were obtained on 160 out of 172 eligible patients from the original trial were enrolled in the follow-up study approximately 8 years after randomization. The follow-up visit consisted of several tests and questionnaires including a clinical exam to determine Expanded Disability Status Score (EDSS) and Multiple Sclerosis Functional Composite (MSFC), and a magnetic resonance imaging exam to calculate the brain parenchymal fraction. Brain parenchymal fraction was correlated with both EDSS and MSFC at each of the four time points for which data were available (baseline 1, 2 and 8 years). Furthermore, the change in BPF was correlated with the changes in disability scores from the end of the phase III trial to the follow-up exam. These data suggest that brain atrophy may be a useful and clinically relevant marker of disease progression in relapsing--remitting MS.

Adjuvants, Immunologic↗

PubMed2000

Self-reported visual dysfunction in multiple sclerosis: results from the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25).

Visual impairment is one of the most common clinical manifestations of Multiple Sclerosis (MS), and is strongly related to overall health-related quality of life (HRQOL) in MS and other disorders. However, the assessment of vision-specific HRQOL in patients with MS has been limited. The purpose of this study was to examine self-reported visual dysfunction in a clinically heterogeneous MS cohort using the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25). The VFQ-25 was administered by telephone interview to a subset of participants in a follow-up study to a phase III trial of interferon beta-1a for relapsing-remitting MS. Mean VFQ-25 composite scores and selected sub-scale scores were significantly lower (worse) among patients in our MS cohort (n=35) compared with a published reference group of patients with no history of chronic eye disease (n= 118). These differences were observed despite a relatively younger age and tighter distribution of binocular visual acuities in the MS cohort Patients with MS in this study thus demonstrated a greater degree of self-reported visual dysfunction, as measured by the VFQ-25, compared with an eye disease-free reference group. The VFQ-25 is a potentially useful measure of vision-specific HRQOL in patients with MS.

Adult↗