Clinical, laboratory, and imaging features generally distinguish neuromyelitis optica from MS. Patients with relapsing optic neuritis and myelitis may have neuromyelitis optica rather than MS. Patients with a relapsing course of neuromyelitis optica have a poor prognosis and frequently develop respiratory failure during attacks of cervical myelitis.
A multiple testing procedure is proposed for comparing two treatments when response to treatment is both dichotomous (i.e., success or failure) and immediate. The proposed test statistic for each test is the usual (Pearson) chi-square statistic based on all data collected to that point. The maximum number (N) of tests and the number (m1 + m2) of observations collected between successive tests is fixed in advance. The overall size of the procedure is shown to be controlled with virtually the same accuracy as the single sample chi-square test based on N(m1 + m2) observations. The power is also found to be virtually the same. However, by affording the opportunity to terminate early when one treatment performs markedly better than the other, the multiple testing procedure may eliminate the ethical dilemmas that often accompany clinical trials.
Objective-To test the hypothesis that magnetic resonance imaging (MRI)-based measurements of hippocampal volume were related to the risk of future conversion to Alzheimer's disease (AD) in elderly patients with a mild cognitive impairment (MCI) Background-Persons who develop AD pass through a transitional state which can be characterized as a MCI. However, in some patients MCI is a more benign condition which may not progress to AD or may do so slowly.
Five procedures are considered for the comparison of two or more multivariate samples. These procedures include a newly proposed nonparametric rank-sum test and a generalized least squares test. Also considered are the following tests: ordinary least squares, Hotelling's T2, and a Bonferroni per-experiment error-rate approach. Applications are envisaged in which each variable represents a qualitatively different measure of response to treatment. The null hypothesis of no treatment difference is tested with power directed towards alternatives in which at least one treatment is uniformly better than the others. In all simulations the nonparametric procedure provided relatively good power and accurate control over the size of the test, and is recommended for general use. Alternatively, the generalized least squares procedure may also be useful with normally distributed data in moderate or large samples. A convenient expression for this procedure is obtained and its asymptotic relative efficiency with respect to the ordinary least squares test is evaluated.
Magnetic resonance imaging(MRI) based volumetric measurements of medial temporal lobe (MTL) structures can discriminate between normal elderly controls and patients with Alzheimer's disease (AD) of moderate to advanced severity. In terms of clinical utility, however, a more important issue concerns the ability of the technique to differentiate between normal elderly controls and AD patients with the very mildest form of the disease. We performed MRI-based volume measurements of the hippocampus, parahippocampal gyrus, and amygdala in 126 cognitively normal elderly controls and 94 patients with probable AD. The diagnosis of AD was made according to NINDS/ADRDA criteria, and disease severity was categorized by Clinical Dementia Rating (CDR) scores. Patients with CDR = 0.5 were classified as very mild, CDR = 1 as mild, and CDR = 2 moderate disease severity.Volumes of each structure declined with increasing age in control subjects and did so in parallel for men and women. The volume of each measured MTL structure also declined with age in patients with AD. The volume of each MTL structure was significantly smaller in AD patients than control subjects (P<.001). Of the several MTL measures, the total hippocampal volume measurements were best at discriminating controls from AD cases. The mean hippocampal volumes for AD patients relative to controls by severity of disease were as follows: very mild AD (CDR 0.5) -1.75 SD below the control mean, mild AD (CDR 1) -1.99 SD, and moderate AD (CDR 2) -2.22 SD. Age and gender adjusted normalized MRI-based hippocampal volume measurements provide a sensitive marker of the MTL neuroanatomic degeneration in AD early in the disease process. KeywordsAlzheimer's Disease; Dementia; MRI; Quantitative MRI; Hippocampus Alzheimer's disease(AD) is the most common cause of dementia in individuals over 60 years of age(1-3). A well accepted biological concomitant of AD is cerebral atrophy(4). The rationale for quantitative magnetic resonance imaging (MRI) of medial temporal lobe (MTL) atrophy in the diagnosis of AD is: 1) A memory impairment is usually the earliest and most severe clinical manifestation of AD; 2) Medial temporal lobe (MTL) limbic structures are central to the integrity of declarative memory function (5); 3) MTL limbic structures are involved earliest and most extensively in the pathology of AD(6,7); and 4) several principal MTL limbic structures are amenable to accurate volumetric quantitation by MRI-the hippocampal 3) Relatively small numbers of subjects were included in individual studies. 4) Rigorous definitions of the severity of AD often were not employed. Most previous studies have included primarily subjects with AD of moderate severity. Consequently, the differences between the AD patients and control subjects with regard to MTL atrophy have been dramatic. The most important test of the utility of the technique would be in patients with very mild AD in whom the diagnostic decision making process is difficult.We report a large series of carefully evaluated and lon...
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