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Biomedical subjects

H J Ader

Publications and source records attributed to H J Ader.

5 recordsLinked to original sources

Patterns of enhancing lesion evolution in multiple sclerosis are uniform within patients.

BACKGROUND: Histopathologic studies suggest that lesion development differs between patients with multiple sclerosis (MS), but that all lesions appear similar within patients. It is unclear whether the same applies to the evolution of lesions on T1-weighted MRI. OBJECTIVE: To evaluate lesion evolution on MRI, comparing variance within and between patients, as well as the relationship between MRI lesion development and clinical characteristics. METHODS: In 48 patients, signal intensity at baseline and at follow-up on T1-weighted MRI of 789 newly enhancing lesions was studied in relationship with clinical data. Patients were included on the basis of showing at least five enhancing lesions that could be followed on monthly scans for 6 months. Variance component analysis and multilevel analysis were used to compare within-patient and between-patient variability. RESULTS: Although various types of lesion evolution could be observed within a single patient, between-patient variance was considerably larger than within-patient variance for MRI parameters used to describe lesion evolution, indicating that lesion evolution is a patient-specific phenomenon. Evolution of lesions in patients with secondary progressive disease more frequently followed a hypointense-hypointense pattern than in patients with relapsing-remitting disease (odds ratio 4.2). Patients with a benign disease course had more persistent isointense lesions at follow-up, whereas patients with aggressive disease had more hypointense lesions. CONCLUSION: Lesion evolution on MRI appears to be a patient-specific phenomenon, although the outcome seems to vary according to the phase and severity of the disease.

Central Nervous System↗

Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination.

OBJECTIVE: The most recent diagnostic criteria for multiple sclerosis (MS) ascertain that findings from spinal cord MRI can be used to demonstrate dissemination in space. Because little is known about the prevalence and characteristics of cord lesions early in the disease, the authors studied the prevalence of spinal cord abnormalities in patients with early-stage MS and assessed their impact on diagnostic classification. METHODS: The brains and spinal cords of 104 recently diagnosed patients with MS were examined. Median interval between first symptom and diagnosis was 18.4 months. The brain MRI protocol included before and after gadolinium axial T1-weighted conventional spin-echo sequences and dual-echo spin-echo images. For spinal cord MRI, sagittal cardiac-triggered dual-echo T2-weighted and sagittal T1-weighted spin-echo images were included. Clinical assessment for each patient included age, sex, clinical signs for spinal cord involvement, and Expanded Disability Status Scale. RESULTS: Abnormal cord MRIs were found in 83% of patients, usually with only focal lesions. Diffuse cord abnormalities were found in 13% of patients, although in isolation they were found in only three patients. Focal cord lesions were often multiple (median number, 3.0), small (median, 0.8 vertebral segments), and primarily (56.4%) situated in the cervical spinal cord. In 68 of 104 patients (65.4%), two or more focal lesions were visible on spinal cord images. The criteria for dissemination in space, as defined in the McDonald criteria for the brain, were met in only 66.3% of the patients. This percentage increased to 84.6% when spinal cord MRI abnormalities were also included. CONCLUSION: Spinal cord abnormalities are prevalent in patients with early-stage MS, have distinct morphologic characteristics, and help to determine dissemination in space at time of diagnosis.

Adult↗

Reproducibility of bone mineral density measurement in daily practice.

BACKGROUND: Bone mineral density (BMD) measurements are frequently performed repeatedly for each patient. Subsequent BMD measurements allow reproducibility to be assessed. OBJECTIVE: To examine the reproducibility of BMD by dual energy x ray absorptiometry (DXA) and to investigate the practical value of different measures of reproducibility in a group of postmenopausal women. METHODS: Ninety five women, mean age 59.9 years, underwent two subsequent BMD measurements of spine and hip. Reproducibility was expressed as smallest detectable difference (SDD), coefficient of variation (CV), and intraclass correlation coefficient (ICC). Sources of variation were investigated by multilevel analysis. RESULTS: The median interval between measurements was 0 days (range 0-45). The mean difference (SD) between the measurements (g/cm(2)) was -0.001 (0.02) and -0.0004 (0.02) at L1-4 and the total hip, respectively. At L1-4 and the total hip, SDD (g/cm(2)) was +/-0.05 and +/-0.04 and CV (%) was 1.92 and 1.59, respectively. The ICC at spine and hip was 0.99. CONCLUSIONS: Reproducibility in the postmenopausal women studied was good. In a repeated DXA scan a BMD change exceeding 2 radical 2CV (%), the least significant change (LSC), or the SDD should be regarded as significant. Use of the SDD is preferable to use of the CV and LSC (%) because of its independence from BMD and its expression in absolute units. Expressed as SDD, a BMD change of at least +/-0.05 g/cm(2) at L1-4 and +/-0.04 g/cm(2) at the total hip should be considered significant.

Absorptiometry, Photon↗

Cardiovascular autonomic function in patients with relapsing remitting multiple sclerosis: a new surrogate marker of disease evolution?

Twenty patients with active relapsing remitting multiple sclerosis (MS) were examined annually for 2 years with a set of autonomic function tests (AFT) consisting of heart rate variability during deep breathing (IE), standing-up, and ratios of Valsalva manoeuvre (VR). Disease characteristics, including T2-weighted magnetic resonance imaging (MRI) of the brain and the expanded disability status scale (EDSS) score were documented each year within 1 week of the AFT. The EDSS score, MRI load lesion and VR did not change significantly over the follow-up period. The IE and initial heart-rate on standing during the first 30 s (DeltaHRMAX) showed significant worsening during follow-up. No relationship was found between deterioration of AFT and EDSS score, number of exacerbations, duration of disease, gender, age, size and number of lesions on MRI. We conclude that patients with active relapsing remitting MS show progression of autonomic dysfunction over a relatively short time. Therefore, in the absence of changes in clinical disability or brain MRI lesion load, AFT might be useful as a sensitive surrogate outcome measure for demonstrating subclinical change in MS.

Adult↗

Exploratory treatment trials in multiple sclerosis using MRI: sample size calculations for relapsing-remitting and secondary progressive subgroups using placebo controlled parallel groups.

OBJECTIVES: Serial brain MRI is widely used in pilot studies of new agents to monitor treatment efficacy in relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS). For pilot trials, sample size calculations for the RR subgroup are based on the data from small numbers of patients and separate calculations for the SP subgroup have not been performed. The present study considers these issues. METHODS: The sample size calculations were based on data from six months of monthly T2 weighted and gadolinium enhanced MRI in 31 RR and 28 SP untreated patients undergoing natural history studies or in the placebo arm of a therapeutic trial. The calculations were for a placebo controlled, parallel groups design lasting six months. The sample sizes were based on bootstrap analysis with an 80% likelihood of showing a given treatment effect. RESULTS: With a single pretreatment scan, demonstration of a 70% reduction in newly active lesions required 2x30 RR and 2x50 SP patients. With an extra run-in scan one month before treatment, the sample sizes were 2x20 for RR and 2x30 for SP patients. CONCLUSIONS: The sample sizes required for RR patients were comparable with previous smaller studies. Larger sample sizes were needed for the SP group, but the extra run in scan resulted in a reduction in both groups. The larger sample sizes in the SPMS group were probably due to the combination of a higher proportion of patients with low MRI activity (< or =2 active MRI lesions in 50% of SP and 32% RR patients), as well as a few patients who displayed extremely high activity, thus increasing interpatient variability. These data should be considered in planning pilot MRI outcome trials.

Adult↗