Faculty Bibliography

BACKGROUND: Multiple sclerosis (MS) can affect virtually every neurological function which complicates the conceptualization and assessment of disability. Similar challenges are encountered in other medical fields including child cognitive development and psychiatry, for instance. In these disciplines progress in diagnosis and outcome measurement has been recently achieved by capitalizing on the concept of bifactor model. OBJECTIVE: To present in accessible terms an application of bifactor confirmatory factor analysis to study the clinical disability outcomes in MS. METHODS: Data included 480 assessments on 301 patients with relapsing-remitting MS who participated in the North American interferon beta-1a clinical trial (Avonex). Measures consisted of the Expanded Disability Status Scale (EDSS), the three components of the Multiple Sclerosis Functional Composite (MSFC), and five other clinical measures of neurological functions. We determined which of three confirmatory factor analysis models (unidimensional, multidimensional, and bifactor) best described the structure of the data. RESULTS: EDSS scores ranged from 0 to 8 (94% between 0 and 4). The final bifactor model fitted the data well, explained 59.4% of total variance, and provided the most useful representation of the data. In this model, the nine measures defined a scoring dimension of global neurological function (63.1% of total composite score variance) and two auxiliary dimensions of extra variability in leg and cognitive function (17.1% and 9% of total composite score variance). CONCLUSION: Bifactor modeling is a promising approach to further understanding of the structure of disability in MS and for refining composite measures of global disability.

Neuromyelitis Optica (NMO) is a potentially devastating, complex autoimmune disease of the central nervous system that differs clinically and pathologically from the more common Multiple Sclerosis (MS). In this paper, we briefly describe our clinical experience with NMO patients treated in an inner city hospital in central Brooklyn, New York, and offer a an up-to-date discussion of diagnosis, treatment, and prognosis of this rare condition

Objective. To compare periventricular lesions in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOsd). Materials and Methods. Sagittal and axial fluid attenuated inversion recovery (FLAIR) sequences of 20 NMOsd and 40 group frequency-matched MS patients were evaluated by two neuroradiologists. On axial FLAIR, periventricular area was characterized as free of lesions/smooth-bordered ("type A") or jagged-bordered ("type B") pattern. On sagittal FLAIR, the images were evaluated for presence of "Dawson's fingers." Results. Type A pattern was observed in 80% of NMOsd patients by Reader 1 and 85% by Reader 2 but only in 5% MS patients by either Reader. Type B was seen in 15% NMOsd patients by Reader 1 and 20% by Reader 2 and in 95% MS patients by either Reader. Dawson's fingers were observed in no NMOsd patients by Reader 1 and 5% by Reader 2. In MS, Dawson's fingers were seen in 92.5% patients by Reader 1 and 77.5% by Reader 2. The differences in periventricular patterns and Dawson's finger detection between NMOsd and MS were highly significant (P < 0.001). Conclusions. Dawson's fingers and "jagged-bordered" periventricular hyperintensities are typical of MS and almost never seen in NMOsd, which suggests a practical method for differentiating the two diseases.

There is an urgent need to develop a practical and reliable clinical measure of disease progression in early and mild MS. We hypothesized that a test of sound lateralization, which is exquisitely sensitive to transmission delays in auditory brainstem, could be more useful for detecting processing speed deficits in mildly impaired MS subjects than standard cognitive tasks. Objective. To develop a practical test of sound lateralization for the clinic and to compare performance of MS subjects with variable disability and healthy subjects on Sound Lateralization Test (SLT) and two speed-of-processing tasks. Design. 42 healthy controls and 90 subjects with clinically definite MS, divided into no, mild, and moderate disability strata, were administered the Symbol Digit Modalities Test (SDMT), and 3-second Paced Auditory Serial Addition Test (PASAT). Results. All of the tests showed an overall difference in performance between controls and the three MS groups, but only the SLT measured a significant difference between controls and the no disability group. Conclusion. SLT is rapidly applied, technically simple, and superior to standard processing speed tests for discriminating between healthy controls and nondisabled MS subjects. SLT should be investigated as an outcome measure in early-phase trials and for monitoring early disease progression in the clinic.

OBJECTIVE: To create a reference table of disability outcomes in multiple sclerosis (MS) that would enable patients to rank their disability relative to others' with similar disease duration and to develop a cost-effective research tool for comparing MS severity across patient populations and time periods. METHODS: The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry collects disability data from patients with MS on a validated, 9-point Patient-Determined Disease Steps (PDDS) scale. We compiled the Disability Expectancy Table, which displays cumulative frequencies of PDDS scores for each year of disease duration, from 0 to 45 years. We also tabulated disease duration-adjusted mean ranks of PDDS scores, referred to as Patient-derived MS Severity Scores (P-MSSS). RESULTS: The cohort consisted of 27,918 NARCOMS enrollees, 72.7% of whom were female and 90.1% of whom were white. Mean age at symptom onset was 30.1 +/- 10.1 years, and age at enrollment was 47.1 +/- 11.0 years. The Disability Expectancy Table and P-MSSS afford a detailed overview of disability outcomes in a large MS cohort over a 45-year period. In the first year of disease, 15% of patients reported need of ambulatory aid, and 4% needed bilateral assistance or worse; after 45 years of disease, 76% of patients required ambulatory aid, and 52% bilateral assistance or worse. Proportion of patients who reported minimal or no interference in daily activities (PDDS